Colunttsia  Winihtv^it^ 
in  ti)t  €it^  of  ^eiti  Iforfe 

CoQege  of  l^f^v^itiani  anb  burgeons; 


3^ef  erence  ILihvaxv 


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THE 

LIVER  OF  DYSPEPTICS 


AND  PARTICULARLY 

THE  CIRRHOSIS  PRODUCED  BY 
AUTOTNTOXICATION    OF    GASTRO-INTESTINAL 

ORIGIN 

(Clinical,  Anatomo-Pathological,  Pathogenic,  and 
Experimental  Study) 


BY 

DR.  J&MILE   BOIX 

Interne  Laureat  des  Hopitaux  de  Paris  (Medaille  d'or,  Concours  de  1893) 
Medaille  d'or  des  Epidemics  (Cholera,  1884) 


AUTHORIZED    TRANSLATION,  FROM    THE 
LATEST    FRENCH    EDITION,  BY 

PAUL  RICHARD  BROWN,   M.D. 

Major  and  Surgeon,  U.  S.  Army 


G.  P.  PUTNAM'S  SONS 

NEW    YORK  LONDON 

27   WEST   TWENTY-THIRD    STREET  24    BEDFORD    STREET,    STRANU 

S^t  ^nicktrbochtt  ^resa 
1897 


COPYRIGHT,  1897 
BY 

G.  P.  PUTNAM'S  SONS 
Entered  at  Stationers'  Hall,  London 


TTbe  ftntcfietbocfier  f>ces0,  "new  Sdrfi 


CONTENTS. 


rAGB 

Introduction  .......«•         i 


PART  I. 

Auto-Intoxication  of  Gastro-Intestinal  Origin        ...••$ 

CHAPTER  I. 
General  Considerations       ....••••  5 

CHAPTER  II. 
The  Poisons  of  the  Alimentary  Canal        .  .  .  .  .  .        lO 

.  CHAPTER  III. 
Conditions  which  Favor  the  Production  of  these  Poisons  .  .  .23 


PART  II. 
The  Liver  of  Dyspeptics    ......••       33 

CHAPTER   I. 

The  Liver  and  its  Poisons  .  ....•••       33 

CHAPTER  II. 
Congestion  of  the  Liver  of  Gastro-Intestinal  Origin.     Clinical  Cases       .  .       36 


iv  Contents. 

CHAPTER  III. 

Confirmed  Cirrhosis  of  the  Liver  Occurring  during  the  Course  of  Dyspepsia, 
Clinical  Cases.  Autopsy  of  Case  of  Dyspeptic  Cirrhosis  of  the  Liver. 
Microscopical  Examination   .......       57 

CHAPTER  IV. 
Etiology  and  Pathogeny  of  Dyspeptic  Cirrhosis  .  ,  .  .81 

CHAPTER  V. 

Pathological  Anatomy  of  Dyspeptic  Cirrhosis  and  its  Place  among  the  Cirrhoses 

of  the  Liver    .........       8q 


PART  III. 


Experimentation      ........ 

Previous  Experiments         ....  ... 

Personal  Experiments  ....... 

SuLstances  Employed :  Butyric,  Lactic,  Valerianic,  Acetic,  Oleic,  Palmitic 
Stearic,  Margaric  and  Oxalic  Acids  ;  Alcohol,  Aldehyde,  Acetone,  Pepper 
Living  Cultures  of  Bacterium  Coli  Communis,  Coli-Toxin  and  Extract  of 
Fasces  ........ 

Recapitulation         ........ 

Conclusions  .  .  .  .  .  .  «  . 


93 
93 
95 

96 
125 
132 


THE   LIVER   OF    DYSPEPTICS 


THE  LIVER  OF  DYSPEPTICS. 


INTRODUCTION. 


The  tendency  of  the  human  mind  is  to  explain  everything  in 
accordance  with  a  single  principle  or  idea.  Nowhere  is  this  truth 
better  exemplified  than  in  our  investigations  of  the  causes  of 
diseases.  For  many  years  has  not  cirrhosis  of  the  liver  been  con- 
sidered as  solely  due  to  the  abuse  of  alcoholic  drinks,  as  if  man 
drank  only  alcohol  and  could  not  sclerose  his  liver  by  other 
ingesta  or  by  substances  not  introduced  from  without  but  gener- 
ated in  the  organism  itself? 

However,  we  have  been  compelled  to  consider  other  patho- 
genic agents  in  certain  cases  in  which  alcohol  could  not  be  impli- 
cated :  lead  poisoning,  syphilis,  impaludism,  and  tuberculosis  have 
contended  with  alcohol  for  a  portion  of  its  illegitimate  domain. 

At  present,  almost  without  exception,  we  still  attribute 
atrophic  cirrhosis  of  the  liver  to  the  excessive  use  of  alcoholic 
beverages  (even  taking  verbatim  its  English  name,  gin-drinker  s 
liver),  and  a  hypertrophic  cirrhosis,  said  to  be  curable,  also  bears 
the  name  of  alcoholic  cirrhosis.  However,  cases  of  hypertrophied 
and  atrophied  livers  are  daily  being  reported  which  cannot  be 
attributed  to  the  abuse  of  alcohol,  as  the  patient  did  not  drink  it 
in  any  form,  and  there  is  now  a  decided  reaction  against  consider- 
ing alcohol  as  the  only  active  agent  in  the  production  of  cirrhosis 
of  the  liver. 

It  is  not  as  a  plea  for  the  innocuousness  of  alcohol  that  I  have 
written  this  work :  all  of  my  readers  who  are  desirous  of  being 
reassured  in  regard  to  the  hepatic  sequelae  of  the  abuse  of  alco- 
holic drinks,  I  refer  to  the  very  interesting  thesis  of  my  colleague 
A.  Lafifitte,^  and  to  a  recent  article  of  A.  Letienne."  I  only  seek 
to  establish  the  fact  that,  in  addition  to  alcohol  and  entirely  inde- 

*  A.  'Ls.^tte^Contribtition  h  V^tude  de  la  cirrhose  de  Laennec,  Paris,  l8g2. 
'  A.  Letienne,  Medecine  moderne,  1894,  No.  15. 


2  The  Liver  of  Dyspeptics. 

pendent  of  it,  independent  also  of  some  hitherto  recognized 
causes  of  hepatic  cirrhosis,  there  is  another  which,  notwithstand- 
ing its  recent  appearance  upon  the  etiological  scene,  we  have 
already  rendered  responsible  for  many  ills,  but  to  which  we  have 
not  yet  thought  of  attributing  an  active  part  in  the  production 
of  sclerosis  of  the  liver:  I  refer  to  auto-intoxication  of  gastro- 
intestinal origin. 

There  is  a  peculiar  form  of  hypertrophic  cirrhosis  which,  in  the 
opinion  of  M.  Hanot  and  myself,  arises  from  the  passage  through 
the  liver  of  toxic  substances  elaborated  in  a  diseased  alimentary 
canal.  This  is  the  only  form  which  we  shall  here  consider,  but 
this  does  not  imply  that  some  other  forms,  even  atrophic,  may 
not  have  the  same  origin. 

It  is  to  be  hoped  that  the  future,  although  laden  with  engage- 
ments almost  innumerable,  as  says  Lasegue,  will  enlighten  us  in 
regard  to  this  important  question.  The  dyspeptic  liver  will  per- 
haps never  have  the  undeserved  renown  of  the  alcoholic  liver,  and 
this  will  be  all  the  better  for  its  reputation.  In  the  etiology  of 
the  cirrhoses,  we  must  put  in  its  proper  place  every  pathogenic 
agent,  whatever  it  may  be,  and  only  accord  efficacious  action  to 
it  when  the  circumstances  prepare  and  favor  this  injurious  action. 
We  cannot  become  cirrhotic  at  will,  even  by  drinking  to  excess, 
even  by  taking  toxic  substances  as  ingesta,  or  by  bringing  on  a 
gastritis  which  permits  abnormal  fermentations  in  the  alimentary 
canal :  if  we  have  not  inherited  the  secret  influence  which  pro- 
duces the  gouty  diathesis,  the  intentional  alcoholic  or  dyspeptic 
only  stands  a  very  great  chance  of  altering  his  hepatic  cells. 

The  gouty  diathesis  is  the  domain  par  excellence  of  the  scle- 
roses, and  predisposition  is  as  indispensable  to  the  greater  part  of 
the  chronic  processes,  as  receptivity  is  essential  in  order  to  con- 
tract the  majority  of  infectious  diseases.  Here  vanishes  the 
dream  of  those  who  are  wedded  to  a  single  cause,  and  who  would 
like  to  reduce  to  a  simple  equation  the  relation  of  a  poison  or  a 
microbe  to  a  given  disease. 

At  the  present  time,  these  ideas  may  appear  hackneyed,  yet 
whenever  pathogeny  is  in  question,  especially  if  we  are  consider- 
ing some  new  cause,  we  permit  ourselves  to  attribute  to  it,  without 
regard  to  the  surrounding  conditions,  the  disease  in  its  totality 
and  even  connect  other  affections  with  it.  I  should  like  to  escape 
this  reproach  and  not  appear  to  see  in  dyspepsia  a  source  of  evils 
for  which  it  is  not  responsible. 


Introduction.  3 

I  employ  the  word  dyspepsia  in  its  broadest  signification,  here 
including  every  defective  functioning  of  the  alimentary  canal, 
whatever  may  be  its  cause,  and  it  is  for  the  sake  of  abbreviation, 
so  to  speak,  that  I  term  the  sclerosis  of  the  liver  which  results 
from  an  auto-intoxication  of  gastro-intestinal  origin,  dyspeptic  cir- 
rhosis. It  is  especially  in  order  to  place  this  form  of  cirrhosis  in 
opposition  to  alcoholic  cirrhosis.  The  term  toxic  cirrhosis  would 
have  been  too  comprehensive,  as  the  toxic  cirrhoses  are  numerous, 
here  including  alcoholic  cirrhosis.  I  desire  then  that  the  terms 
dyspeptic  liver  and  dyspeptic  cirrhosis  be  only  considered  as  a 
handy  means  of  expression  and  also  as  a  means  of  abbreviation. 

Prior  to  our  taking  up  the  study  of  the  clinical  forms,  which 
is  the  subject  of  the  principal  portion  or  this  work,  it  is  essential 
that  a  sort  of  general  picture  should  be  presented  of  the  patho- 
genic elements  concerned.  To  this  I  have  devoted  the  first  part, 
which  includes  three  chapters ;  one  treating  of  auto-intoxication 
of  gastro-intestinal  origin,  another  enumerating  the  products  of 
fermentation  capable  of  exercising  a  pathogenic  action,  and  last 
of  all,  a  glance  at  the  conditions  which  favor  abnormal  fermenta- 
tions and  the  production  of  these  poisons. 

In  a  second  part,  after  some  preliminarj^  considerations  in  re- 
gard to  the  anti-toxic  role  of  the  liver,  comes  the  history  of  the 
dyspeptic  liver  with  its  two  forms,  congestion  and  cirrhosis. 
Next  I  consider  the  anatomical  form  of  dyspeptic  cirrhosis  and 
its  place  among  the  scleroses  of  the  liver. 

The  third  part  is  devoted  to  the  relation  of  my  personal  ex- 
periments with  some  of  the  agents  h  priori  suspected  as  causes  of 
gastro-intestinal  fermentations,  and  the  successful  results  of  which 
will  show,  as  I  hope,  the  legitimate  influence  which  the  dyspep- 
sias may  claim  in  the  etiology  of  the  cirrhoses  of  the  liver. 


PART  I. 
Auto-Intoxication  of  Gastro-Intestinal  Origin. 


CHAPTER  I. 

GENERAL  CONSIDERATIONS. 

"  In  the  normal  as  well  as  in  the  pathological  condition,  the 
organism  is  a  receptacle  and  laboratory  of  poisons"  (Bouchard*). 
With  a  precision  which  is  almost  mathematical,  the  learned 
work  of  the  eminent  professor  develops  this  fatal  aphorism ;  the 
secret  of  the  disturbances  of  the  organism,  and  also  perhaps 
the  secret  of  their  relief. 

Toxicology  is  becoming,  as  it  were,  almost  the  whole  science 
of  medicine,  as  it  is  extending  its  domain  beyond  the  mineral  and 
vegetable  world ;  and  it  is  to  be  hoped  that  it  will  inform  us  in 
regard  to  the  various  microbian  poisons  and  their  effects,  and  will 
also  demonstrate  to  us  how  we  may  be  able,  by  opposing  other 
poisons  to  these  poisons,  to  neutralize  or  weaken  their  action ; 
for  every  medicine  is  a  poison  and  every  poison  a  medicine. 

Owing  to  the  powerful  impulse  given  to  it  by  M.  Bouchard, 
the  doctrine  of  auto-intoxication  is  now  dominant  in  pathology, 
with  the  exception  of  such  diseases  as  arise  from  exogenous  in- 
toxications and  from  specific  infections ;  and  even  these  are  fre- 
quently seconded  by  auto-intoxication.  This  term  is  difficult  to 
define,  not  that  we  do  not  understand  its  signification,  but  because 
we  cannot  exactly  state  its  precise  limits. 

Must  we  only  accept  the  word  in  its  literal  sense  and  solely 
connect  with  it  the  poisons  fabricated  in  our  organism  and  by  its 
cells  alone  ?  Or  shall  we  consider  as  autochthonous  poisons  all 
those  which  originate  within  us,  whether  they  proceed  from  our 
elementary  organs  (organites)  or  from  their  habitual  guests,  the 
micro-organisms  ?      The  latter  interpretation,  both  broader   and 

^  Bouchard,  Lefons  sur  les  auto-intoxications  dans  les  maladies,  Paris,  18S7, 

5 


6  The  Liver  of  Dyspeptics. 

truer,  appears  to  be  in  accordance  with  the  majority  of  patholog- 
ical processes,  as  frequently  it  is  impossible  to  give  to  each  of 
these  poisons  of  different  origin  its  due  share  in  the  production 
of  disease.  This  is  the  generally  received  opinion  and  is  also  that 
of  M.  Bouchard,  who  explains  it  very  clearly. 

Now,  in  what  part  of  the  human  organism  can  these  poisons 
be  found  in  greater  quantity  than  in  the  alimentary  canal,  espe- 
cially when  there  is  any  interference  with  its  normal  functions? 
"  We  have  certainly  accepted  the  fact,  not  without  some  difficulty 
however,"  says  M.  Bouchard,*  "  that  certain  general  accidents 
may  result  from  disease  of  the  kidneys,  and  I  am  of  the  opinion 
that  the  functional  dignity  of  these  organs  is  less  than  that  of  the 
alimentary  canal ;  they  excrete  matter  without  modifying  it,  and 
yet  how  many  disturbances  their  diseases  produce  in  the 
organism  ? 

"  What  may  not  take  place  when  the  stomach  is  diseased,  the 
functional  derangement  of  which  throws  the  whole  intestine  into 
disorder?  Why  does  not  its  derangement  react  upon  the  whole 
organism  ?  Think  of  the  physiological  importance  of  the  alimen- 
tary canal ;  it  introduces  every  substance  solid  and  liquid  into  the 
body,  save  oxygen,  and  before  introducing  matter,  it  must  elabo- 
rate it.  It  does  not  then  play  simply  an  excretive  role :  its 
improper  functioning  must  affect  certain  emunctory  apparatuses 
and  the  cells  of  the  whole  organism." 

This  idea  is  certainly  not  a  modern  one,  since  it  dates  back 
to  the  time  of  Hippocrates,''  who  was  of  the  opinion  that  the 
stomach  bears  the  same  relation  to  animals  as  the  soil  does 
to  plants  :  ut  in  arboribus  terra,  sic  in  animalibus  alvus  succum 
alibilem  suppeditat.  From  whence  it  follows,  says  Beau,  that  the 
man,  whose  digestion  is  defective,  is  comparable  to  a  tree  which, 
planted  in  sterile  soil,  finishes  by  withering  and  perishing.  Mor- 
boruin  fere  omnium  causa  est  stomachi  infirmitas,  also  says  Bene- 
detti.'  We  know,  moreover,  the  excessive  importance  which 
Broussais  attached  to  gastro-enteritis,  and  it  is  almost  Broussism 
which  is  springing  up  to-day  in  another  form. 

Beau*  more  than  merely  calls  attention  to  the  fact  that  dele- 
terious products  may  be  elaborated  by  a  diseased  stomach,  for  he 

'Bouchard,  loc.  ciL,  p.  i8i. 

*  Hippocrates,  De  hunioribus,  cap.  iv. 

*  Alexander  Benedictus,  Opera,  p.  1125,  Basileas,  1539. 
^Beau,  Traite  de  la  dyspepsie,  Paris,  1866,  p.  37. 


General  Considerations.  7 

says  :  "  When  these  symptoms  occur  during  the  act  of  digestion,  we 
may  always  ask  ourselves  if  they  depend  upon  a  purely  sympathetic 
irritation  or  possibly  upon  an  irritant  digestive  product  carried  to 
a  greater  or  less  distance  from  the  stomach  by  the  circulation. 

"  To  a  great  extent  certain  of  these  symptoms  are  connected 
with  the  alteration  of  the  blood  which  follows  the  dyspeptic  con- 
dition." The  systematic  investigation  made  by  Beau  in  regard  to 
these  alterations  of  the  blood  illy  accords  with  late  discoveries; 
but  his  doctrine  of  a  chylopathy  causing  the  hemopathic  series  of 
dyspeptic  disturbances  is  not  displeasing  to  modern  humoralism. 

The  list  of  accidents  and  symptoms  is  long,  which  modern 
writers  attribute  to  auto-intoxication  of  gastro-intestinal  origin, 
and  the  theory  of  Beau  in  regard  to  the  diseases  which  are  con- 
nected with  dyspepsia  does  not  now  appear  so  ridiculous.  M. 
Bouchard  derives  from  it  "  accidents  so  varied  and  multiple,  that 
their  enumeration  at  first  sight  provokes  our  incredulity."  Besides 
those  affecting  the  alimentary  canal  and  the  liver,  in  regard  to 
which  farther  on  we  will  find  more  details,  there  is  a  whole  series 
of  accidents  remote  from  the  dyspepsias;  those  which  we  have 
hitherto  considered  as  reflexes  and  which  really  are  of  toxic  origin. 

Nervous  Accidents. — Exhaustion  on  awakening,  headache,  sad- 
ness, irritability,  sensitiveness  to  cold,  sleeplessness,  vertigo, 
disturbances  of  vision,  hallucinations,  partial,  and  temporary  numb- 
ness of  the  limbs,  contraction  of  the  extremities,  transient  aphasia, 
fainting,  palpitation  of  the  heart,  pseudo  angina  pectoris,  night 
sweats,  intercostal  neuralgia. 

Cutaneous  Accidents. — Alteration  of  the  secretion  of  the  sudori- 
parous and  sebaceous  glands,  eruptions  such  as  eczema,  pityriasis 
versicolor,  urticaria,  acne. 

Renal  Accidents. — Albuminuria,  peptonuria. 

Accidents  Affecting  the  General  Nutrition. — Loss  of  strength, 
lessening  of  physical  and  mental  vigor,  emaciation,  etc.  ;  the 
osseous  system  itself  is  not  spared,  and  manifests  its  suffering 
by  enlargement  of  the  base  of  the  second  phalanx  (nodosities  of 
Bouchard),  and  sometimes  by  osteomalacia. 

According  to  M.  Comby,^  dyspepsia,  in  its  broadest  sense,  is 
the  cause  of  rickets  (dissolving  action  of  the  acids  of  fermenta- 
tion :  lactic,  acetic,  etc.).     A  pupil  of  these  two  physicians  ^  has 

*  Comby,  Traite  du  rachitisme,  Paris,  1892. 
^  Rene  Millon,  These  de  Paris,  1893. 


8  The  Liver  of  Dyspeptics. 

written  a  thesis  in  regard  to  the  cutaneous  manifestations  due  to 
improper  nutrition  in  children,  in  which  digestive  disturbances 
take  a  prominent  part  in  the  etiology. 

Lastly,  according  to  M.  Bouchard,  several  diseases  are  occa- 
sionally due  to  the  gastropathies :  chlorosis,  pulmonary  phthisis, 
typhoid  fever.'  For  M.  Bazy,^  gastrectasia  would  play,  in  the 
genesis  of  the  complications  of  wounds,  accidental  or  surgical,  a 
role  analogous  to  that  of  alcoholism,  impaludism,  diabetes,  etc. 
In  the  gastric  disease  called  "  permanent  hypersecretion  or 
Reichmann's  disease,"  Bouveret  and  Devic'  have  studied  the 
pathogenesis  of  tetany,  already  well  known  through  the  labors 
of  Neumann,  Kussmaul,  Galliard,  Laprevotte,  Dujardin-Beau- 
metz,  etc. 

From  the  products  of  digestion  collected  for  a  month,  they 
have  succeeded  in  preparing  an  alcoholic  extract  producing  a 
marked  convulsive  action  upon  animals ;  they  also  attribute 
tetany  to  intoxication  of  gastric  origin.  Debove  and  Remond* 
have  not  been  able  to  verify  the  assertions  of  Bouveret  and 
Devic.  But  very  recently,  E.  Cassaet  and  G.  Ferr6  (of  Bordeaux)^ 
investigating  from  this  point  of  view  the  gastric  juice  of  a  hyper- 
peptic,  who  never  had  manifested  any  symptoms  of  tetany,  have 
been  able  to  provoke,  with  the  rabbit,  in  numerous  experiments, 
very  violent  convulsive  phenomena  :  they  add  that  the  substance 
extracted  from  hyperchlorhydric  stomachs  is,  besides,  vaso-con- 
strictor,  myositic,  anaesthetic,  and  immediately  dyspnoeic. 

Brieger*  had  previously  isolated,  in  the  products  of  the  diges- 
tion of  albuminoid  matters,  a  substance  likewise  convulsive, 
pepto-toxin,  corresponding  chemically  to  the  bodies  of  the  series 
CnHgN+iNOg.  The  tetanizing  poison  of  Bouveret  and  Devic  is 
different  from  this  pepto-toxin.  These  authors  also  attribute  to 
it  the  gastric  epilepsy,  the  so-called  congestive  epilepsy,  observed  by 
Pommay,^  especially  with  plethoric  people  and  great  eaters,  as 
the  result  of  errors  of  diet,  of  large  meals,  and  of  the  abuse  of 
alcoholic  drinks.  The  latest  utterance  in  regard  to  poisoning 
by  the  toxic  substances  of  the  intestinal  tract  is  the  comatose 

'  P.  Le  Gendre,  Dilatation  de  Vestomac  et  Jievre  typhoide,  Paris,  1886. 

*  Bazy,  Arch.  gdn.  de  me'decine,  mars,  1889. 

"  Bouveret  et  Devic,  Revue  de  m^deciiie,  Janvier  et  fevrier,  1892. 

^  Debove  et  Remond,  Traits  des  maladies  de  Vestomac,  p.  366,  Paris,  1894. 

^  Cassaet  et  Ferre,  Soc.  de  biologic,  23  juin,  1894. 

*  Brieger,  Microbes,  ptomaines  et  maladies,  Paris,  1887. 
'  Pommay,  Revise  de  medecine,  1881,  p.  449. 


General  Considerations.  9 

condition  observed  by  von  Jaksch,  who  compares  it  to  diabetic 
coma. 

Litten  '  has  noticed  it  in  grave  dyspeptic  conditions,  and  has 
described  it  under  the  name  of  dyspeptic  coma.  Stadelmann,* 
Minkowski/  Lepine,*  attribute  it  to  an  acid  dyscrasia,  of  which 
one  of  the  principal  factors  is  probably  oxybutyric  acid.  Now, 
in  the  urine  of  patients  affected  with  cancer  of  the  stomach, 
Klemperer  *  has  found  this  acid,  von  Jaksch  some  acetic  acid,  and 
Senator  a  marked  quantity  of  indican,  which  results  from  the 
putrefaction  of  albuminoids  in  the  stomach  and  intestines.  By 
the  side  of  dyspeptic  coma  we  should  place  that  which  Humbert 
has  called  intestinal  septiccBmia. 

Here  then  is  a  true  Iliad  of  evils  chargeable  to  auto-intoxica- 
tion of  gastro-intestinal  origin.  As  far  as  the  conditions  of  our 
chemical  and  bacteriological  knowledge  will  permit,  we  should 
now  study  the  normal  and  abnormal  products  of  the  alimentary 
canal,  as  well  as  the  factors  of  these  products,  the  microzoa,  guests 
of  the  mouth,  the  stomach,  and  the  intestines.  But  in  order  to 
take  into  consideration  all  the  poisons  which  may  be  encountered 
in  the  digestive  system,  it  is  essential  to  enumerate  those  which, 
under  a  disguised  form,  are  introduced  in  our  food  ;  their  role  is 
not  unimportant,  whether  they  act  by  themselves  or  whether 
they  produce  a  disturbance  of  the  digestion  capable  of  giving  rise 
to  other  toxic  substances. 

^  Litten,  Berliner  klin.   Woe  kens  chr.,  1882. 

^  Stadelmann,  Arch.f.  exp.  Pathol.,  Bd.  xvii.,  p.  419. 

^  Minkowski,  Berlin,  klin.   Woch.,  1887. 

*  Lepine,  Revue  de  mddecine,  mars,  1887. 

*  Klemperer,  Berlin,  klin.   Woch.,  1889. 


CHAPTER   II. 

THE   POISONS   OF   THE   ALIMENTARY   CANAL. 

Poisons  of  Alimentary  Origin. — The  history  of  botulism,  which 
commences  in  1735,  in  connection  with  poisoning  by  sausages,  is 
now  too  well  known  for  it  to  be  necessary  for  me  to  dwell  upon 
it.  The  researches  of  Hoppe-Seyler,  Brouardel,  and  Boutmy, 
Gaspard  and  Panum,  Bouchard,  Selmi,  Gautier,  etc.,  have  shown 
that  the  accidents  due  to  the  ingestion  of  spoiled  pork,  pickled 
goose,  and  decomposed  meats  in  general  are  caused  by  very  toxic 
alkaloids. 

Fish,  lobsters,  oysters,  snails,  mouldy  bread,  cheese,  and  putrid 
water  also  frequently  contain  analogous  poisons.  A  list  of  them 
may  be  found  in  the  work  of  M.  Charrin:  "  Poisons  of  the  Organ- 
ism. "  *  Microbes  are  not  lacking  in  the  ingesta.  Speaking  only 
of  bread,  it  may  contain,  even  when  in  a  good  condition  of  pre- 
servation, the  Penicillium  glaucum,  the  Ascophora  nigricans,  the 
Oidium  aurantiacum,  and  the  Mucor  i^nucedo. 

As  to  water,  even  potable,  I  will  not  undertake  an  enumera- 
tion of  the  micro-organisms  which  may  be  present  in  it :  however 
we  must  not  forget  the  typhoid  bacillus  and  the  Bacterium  coli. 
There  are  in  bread,  especially  in  the  soft  part,  some  substances 
which  farther  on  we  shall  see  are  injurious,  if  they  are  present  in 
sufficient  quantity.  Bread  fermentation  affects  two  elements: 
starch  and  gluten.  Starch,  in  presence  of  diastase,  is  split  up  inta 
maltose  and  dextrin. 

Maltose,  under  the  influence  of  Saccharomyces  minor,  furnishes 
two  sugars,  dextrose  and  levulose,  which  ferment  in  their  turn  in 
order  to  produce  alcohol  and  carbonic  acid  (Graham).  Gluten,  in 
the  presence  of  the  Bacillus  glutinis,  during  the  baking  of  bread, 
gives  off  some  acetic,  butyric,  and  lactic  acids.  We  also  find  in 
bread  some  leucin,  tyrosin,  and  phenol — that  is,  the  products  of  the 
fermentation  of  a  nitrogenous  substance  (Chicaudart).  Even  in 
the  centre  of  the  loaf,  the  Bacillus  glutinis  resists  the  elevated 

'  Charrin,  EncyclopMie  LMut/,  Masson,  Paris,  1893. 
10 


Alimentary  Poisons.  1 1 

temperature  of  the  oven  and  may  continue  the  acetic  fermentation 
in  the  stomach  (Bouchard).' 

"  With  certain  persons,"  says  M.  Bouchard,  "  some  particular 
foods,  without  being  in  any  respect  toxic  or  putrid,  invariably 
cause  indigestion  and  various  grave  phenomena.  In  such  a  case, 
if  there  is  poisoning,  it  is  the  fault  not  of  the  food,  but  of  the 
non-digestion;  the  gastric  juice  will  not  transform  a  food  which 
the  stomach  does  not  care  to  receive ;  the  nervous  system  pro- 
duces secretory  disturbance  and  the  gastric  juice  ceases  to  flow 
into  the  stomach,  or  possibly  hydrochloric  acid  is  absent  from  it 
at  the  moment  of  the  conflict  of  the  food  with  the  microbes. 
Abnormal  fermentations  take  place  in  the  stomach  and  intestine  ; 
the  toxic  products  of  these  fermentations  are  absorbed ;  thence 
poisoning  results." 

This  is  not  a  simple  hypothesis,  since,  in  a  case  of  this  kind, 
M.  Bouchard  has  been  able  to  ascertain  the  quantity  of  the  mi- 
crobes present  in  a  third  of  the  faeces,  which  contained  fifteen  mil- 
ligrams of  alkaloids  per  kilogram.  There  was  also  found  in  the 
urine  an  amount  of  alkaloids  fifty  times  above  the  normal,  and 
this  through  the  multiplication  alone  of  the  normal  bacteria  of 
the  alimentary  canal. 

Poisons  Fabricated  in  the  Alimentary  Canal. — It  is  now  posi- 
tively established  that,  as  Prout  claimed  in  1824,'  and  as  Richet 
and  Berthelot  have  especially  proven,  the  normal  acid  of  the  gas- 
tric juice  is  a  mineral  acid,  hydrochloric  acid.  Let  this  acid  be 
set  free  secondarily  in  the  stomach,  by  m_eans  of  its  secretion  of 
alkaline  chlorides,  as  Hayem  and  Winter  have  claimed,  or  that, 
as  Ewald,^  Martins,  and  Luttke  have  shown,*  it  results  directly 
from  glandular  functioning  (parietal  cells  of  Heidenhain  or  delo- 

*Very  recently  Walsh  (British  Medical  Association,  session  of  1894)  has  proven 
that  bread,  fresh  from  the  oven,  is  not  sterile,  and  that  a  goodly  number  of  micro- 
organisms, and  especially  spores,  situated  in  the  centre  of  the  loaf,  resist  the  high 
temperature  of  the  oven.  He  propounds  the  question,  whether  bread  in  such  a  case 
would  not  be  an  excellent  medium  for  the  propagation  of  disease  and,  especially,  of 
gastro-intestinal  affections. 

George  Brown  is  of  the  same  opinion,  and,  in  certain  choleriform  affections,  of 
which  he  has  endeavored  to  ascertain  the  cause,  he  has  been  led  to  incriminate  the 
bread  ingested,  and  has  finally  discovered  that  the  flour  employed  in  its  manufacture 
was  damaged. 

2  Prout,  Phil.  Trans.,  1824. 

^Ewald,  Zeitschrift  f.  klin.  Med,,  1892. 

^Martins  and  Luttke,  Die  Magensaure  des  Menschen.  Stuttgart,  1892. 


1 2  The  Liver  of  Dyspeptics. 

morphous  cells  of  Rollet)/  makes  but  little  difference ;  all  that  is 
necessary  for  us  to  remember  is  that  normally  there  is  in  the 
stomach  no  other  acid  than  hydrochloric  ;  or  rather  that  this 
alone  is  necessary  for  digestion.  Whence  it  follows  that  the  or- 
ganic acids  which  may  there  be  encountered  are  at  least  useless 
if  not  injurious.  But  before  saying  anything  in  regard  to  them, 
it  will  be  well  to  consider  the  variations  of  the  hydrochloric  acid 
of  the  stomach,  it  having  been  considered  as  an  antiseptic  op- 
posing itself  to  the  production  of  organic  acids  and  abnormal  fer- 
mentations. In  fact,  this  is  what  the  experiments  in  vitro  of  Cohn 
and  Hirschfeld,''  Strauss  and  Wurtz,  have  appeared  to  demonstrate. 

If  the  gastric  juice  of  the  dog  or  of  man,  which  contains  in  the 
normal  state  an  infinite  number  of  microbes,  is  infected  inside  of 
twenty-four  hours  after  its  extraction,  in  a  few  days  the  colonies 
there  developed  are  innumerable ;  with  gastric  juice  four  days  old, 
they  are  still  present  in  considerable  number  (675  in  an  Esmarch 
tube)  ;  their  development  is  only  completely  prevented  with  gastric 
juice  eight  days  old. 

A  certain  time,  shorter  or  longer,  is  then  necessary  to  enable 
the  gastric  juice  to  destroy  the  microbes  and  the  germs  which  it 
contains.  Hydrochloric  acid  diluted  with  water  in  the  same 
proportion  in  which  it  is  found  in  the  various  gastric  juices, 
comports  itself,  from  this  point  of  view,  almost  exactly  the  same 
as  the  gastric  juice  itself.  But  what  shall  we  think  in  regard  to 
the  anti-fermentative  action  of  a  gastric  juice  diluted  by  foods 
and  drinks,  especially  at  a  time  when  the  microbes  are  more  or 
less  inclosed  in  animal  and  vegetable  tissues  and  in  part  protected 
by  them  ? 

Also  both  MM.  Strauss  and  Wurtz  acknowledge  that  in  their 
experiments  "  the  antiseptic  effect  obtained  is  a  maximum,  effect 
which  is  never  realized  in  physiological  digestion  in  the  same  pro- 
portions." According  to  Miller,  there  are  at  least  two  parts  per 
thousand  of  HCl  necessary  in  order  to  arrest  the  fermentations 
produced  by  the  microbes  which  he  has  found  in  the  digestive 
passages.  We  are  then  obliged  to  consider  the  antiseptic  role  of 
hydrochloric  acid  as  comparatively  unimportant,  and  we  have  not 
the  right  to  conclude  on  the  greater  or  less  probability  of  abnormal 
fermentations  in  a  stomach,  according  to  the  quantity  of  hydro- 

*  Swiccicki  and  de  Sehrwald,  Munch,  med.   Wochenschrift,  No.  ii,  1889. 
^  Strauss  et  Wurtz,  Arch  de  mM.  expdrimen.,  i88g,  p.  370. 


Alimentary  Poisons.  13 

chloric  acid  which  it  contains.  Experiments  likewise  have  well 
demonstrated  this  fact. 

Lesage/  comparatively  examining  the  micro-organisms  of  a 
certain  number  of  stomachs  variously  affected,  has  arrived  at  this 
conclusion,  apparently  paradoxical  ;  that  there  are  few  microbes 
in  hypo-cJilorJiydric  stomachs,  and  that  there  is  a  much  greater 
number  of  them  in  hyper-cJilorJiydric  stomachs.  Now,  these  are 
the  microbes  which  produce  fermentations.  Bouveret  ^  a  long  time 
previously  had  noticed  that  microbes  were  present  in  liquids  re- 
moved from  stomachs  affected  with  permanent  hypersecretion, 
and  Mathieu  and  Remond  ^  had  ascertained  that,  in  the  dilated 
stomachs  of  individuals  secreting  hydrochloric  acid  in  excess,  the 
organic  acids  of  fermentation  attain  a  figure  as  high  as  in  cancer- 
ous stomachs  devoid  of  hydrochloric  acid.  Soupault"  has  fre- 
quently observed  the  same  thing.  Ferinentations  are  then  frequent 
in  all  the  varieties  of  gastric  chemism. 

It  was  important  to  establish  this  fact  in  the  first  place. 

Lactic  Acid. — We  have  above  seen  that  a  certain  quantity  of 
lactic  acid  is  borne  into  the  stomach  by  the  crumb  of  bread  ;  there 
is  also  a  considerable  proportion  of  it  (sarco-lactic  acid)  in  the  lean 
meat  taken  as  food.  Lastly,  it  proceeds  from  the  buccal  fermen- 
tation of  amylaceous  foods  under  the  influence  of  the  ptyalin  con- 
tained in  the  saliva,  and  of  the  Bacillus  lactique  of  Pasteur  (or  of 
a  bacillus  very  similar  and  endowed  with  the  same  property),  which 
Miller '  has  found  in  the  mouth. 

Besides,  a  certain  number  of  microbes  introduced  into  mediums 
containing  carbo-hydrates  there  develop  a  fermentation  of  which 
one  of  the  products  is  lactic  acid.  The  lactic  fermentation  trans- 
forms milk  sugar  into  lactic  acid,  the  milk  sugar  passing  in  the 
first  place  probably  into  the  state  of  glucose  of  which  two 
molecules  give  four  of  lactic  acid. 

2(CeH,20e)  =  4(C3He03). 

This  acid  is  found  in  the  stomach  and  is  there  found  alone  at  the 
commencement  of  digestion.     In  proportion  as  HCl  is  secreted, 

^  Lesage,  cit^par  Hay  em,  Lemons  de  thirapeutiqtie,  4  serie,  p.  201. 

'  Bouveret,  Traits  des  maladies  de  I'estomac,  1893,  p.  132. 

3  Mathieu  et  Remond,  Soc.  med.  des  hopitaux,  1892. 

^  Soupault,  "  Des  dyspepsias  nerveuses,"    These  de  Paris,  1893,  p.  35. 

*  Miller,  Die  Microorganismen  der  Mundhole,  Leipzig,  1889. 


14  The  Liver  of  Dyspeptics. 

the  lactic  acid  diminishes  and  finally  completely  disappears.  This 
fact  has  been  demonstrated  by  Ewald  and  Boas/  who  distinguish 
three  periods  in  the  digestion  of  a  mixed  meal : 

Pure  lactic  acid  stage 50  to  60  minutes. 

Lacto-hydrochloric  acid  stage 60  to  70  minutes. 

Pure  hydrochloric  acid  stage Until  the  end. 

After  the  test  meal  of  Ewald,  it  is  seldom  that  the  proportion  of 
lactic  acid  encountered  with  a  healthy  man  exceeds  o.i  to  0.3  p. 
1000 ;  there  is  generally  no  decided  reaction  with  Uffelmann's 
solution  ;  a  quantity  sufficient  to  produce  the  characteristic  yellow 
coloration  is  an  indication  of  a  pathological  condition  and,  say 
Debove  and  Remond,  very  frequently  of  cancer  of  the  stomach. 

Lactic  acid,  even  in  the  form  of  lactate  of  soda,  is  toxic. 
Klein,''  a  pupil  of  Lupine,  with  the  guinea-pig,  has  been  able  to 
produce  death  with  a  dose  of  about  a  gram  and  a  half  per  kilo- 
gram of  weight.  MM.  Bourget  and  Fremont^  think  that  by 
itself  alone  lactic  acid  may  produce  pyrosis.  We  shall  see  further 
on  how  it  affects  the  liver. 

Acetic  Acid. — In  this  respect  it  is  the  same  with  acetic  acid. 
This  acid  (or  its  ethers),  the  odor  of  which  is  easily  recognizable,  is 
present  in  large  quantity  in  matters  vomited  during  indigestion  ; 
we  encounter  it  in  the  stomach  of  alcoholics  and  dyspeptics. 

It  is  owing  to  the  Mycoderma  aceti  that  the  alcohol  is  trans- 
formed into  acetic  acid. 

C3H60+20=   H2O  +  C2H4O2. 

This  transformation  cannot  take  place  in  the  stomach,  as  it  ceases 
at  35°  C.  But  acetic  acid  is  an  accessory  product  of  the  lactic 
fermentation  of  carbo-hydrates,  and  consequently  we  always  find 
it  associated  with  lactic  acid  in  the  vomited  matters  of  infants  at 
the  breast. 

Bouveret  *  has  remarked  that  the  acetic  fermentation  rather 
accompanies  the  dilatations  with  hypersecretion,  whilst  the 
butyric  fermentation  is  usually  encountered  in  cases  of  diminu- 
tion of  the  secretion  of  hydrochloric  acid.  This  observation,  he 
says,  coincides  with  the  results  of  the  experiments  of  M.  Paschutin, 
which  demonstrate  that  HCl  arrests  the  butyric  fermentation. 

'  Ewald  and  Boas,  Virchow's  Arckiv,  Bd.  C  et  CI. 

®  Klein,  "  De  la  fatigue  et  du  surmenage,"  Th.  de  Lyons^  1886. 

^Bourget  et  Fremont,  cites  par  Soupault,  loc.  cit.,  p.  48. 

*  Bouveret,  loc.  cit.,  p.  125. 


Alimentary  Poisons,  15 

Butyric  Acid. — The  sharp  and  nauseous  odor  of  this  acid  is 
particularly  well  known  to  dyspeptics.  This  odor  is  so  pene- 
trating that  in  the  open  air  a  drop  of  it  can  be  smelled  at  some 
distance  and  for  several  hours. 

It  is  synonymous  of  abnormal  fermentation ;  its  presence  in 
the  digestive  liquids,  especially  in  appreciable  quantity,  is  in  some 
sort  pathognomonic.  The  agents  of  the  butyric  fermentation 
are  numerous  ;  we  know  the  principal  ones  :  the  Bacillus butyricus 
of  Pasteur  or  Clostridium  butyricum  of  Prazmowski,  the  Bacillus 
amylobacter  of  Tr^cul  and  Van  Tieghem,  the  Bacillus  butylicus  of 
Fitz.  All  these  organisms  are  anaerobic ;  their  action  is  also 
favored  by  the  presence  of  the  Bacillus  lacticus  which  absorbs 
oxygen. 

In  fact,  the  lactic  fermentation  precedes  the  butyric  and  it  is 
upon  the  lactic  acid  that  the  anaerobic  bacilli  act,  giving  off 
butyric  acid,  carbonic  acid  gas,  and  hydrogen  : 

2(C3H,03)  =  C.HgOa  +  2CO3  +4H. 
The  hydrogen  which  we  find  in  dilated  stomachs  proceeds  from 
this  reaction.      O.  Weber  has  noticed  that  cats  are  very  sensitive 
to   the  action  of   butyric   acid   and    Meyer'  has  confirmed  this 
observation. 

Valeric  or  Valerianic  Acid. — This  acid  has  been  only  rarely 
observed  in  gastric  liquids ;  undoubtedly  because  we  seldom  seek 
for  it.  It  is  likewise  quite  difficult  to  distinguish  from  butyric 
acid,  to  the  series  of  which  it  belongs.  It  is  a  product  of  the 
oxidation  of  amylic  alcohol,  which  drunkards  frequently  ingest  in 
large  quantity.  Leucin,  a  product  of  the  putrefaction  of 
albuminoid  matters,  also  easily  gives  rise  to  valeric  acid, 
especially  in  an  alkaline  medium,  as  it  is  a  residue  of  defective 
digestion. 

Propionic  Acid. — This  acid  has  sometimes  been  found  in  the 
gastric  juice  and  particularly  in  that  removed  from  the  stomachs 
of  individuals  suffering  from  dilatation  (Debove  and  R6mond). 
We  never  look  for  it  in  the  ordinary  examination  of  the  contents 
of  the  stomach.  It  is  the  homologue  immediately  superior  of 
acetic  acid.  In  an  alkaline  medium  it  arises  in  the  oxidation  of 
sugar,  starch,  gum,  alcohol,  and  acetone.  Meyer  has  observed 
that  the  propionate  of  soda,  in  the  dose  of  a  gram  to  the  kilo- 
gram of  weight,  produces  great  somnolence  with  the  cat. 

*  Meyer,  "  Recherches  sur  Taction  toxique  de  quelques  acides  de  la  serie  grasse," 
Arch.  /.  exp.  Pathol. ,  Bd.  xviii. 


1 6  The  Liver  of  Dyspeptics 

Fatty  Acids. — Oleic,  palmitic,  margaric,  and  stearic  acids  are 
ingested  with  all  the  fats.  They  are  found  in  great  quantity  in 
the  alimentary  canal  where  saponification  takes  place.  But  they 
may  be  set  free  in  stomachs  the  seat  of  putrefaction.  They  only 
appear  to  have,  from  a  toxic  or  irritant  point  of  view,  a  very 
slight  importance,  as  we  shall  see  in  the  experimental  portion  of 
this  work ;  but  their  presence  in  the  stomach  contributes  to 
promote  the  abnormal  fermentations. 

Oxalic  Acid. — This,  certainly,  is  a  poison.  It  exists  in  the 
organism  in  the  state  of  oxalate  of  calcium,  and  passes  unper- 
ceived  during  a  condition  of  health,  as  it  is  destroyed  in  the  blood, 
where  it  passes  into  the  condition  of  urate,  and  is  eliminated  by 
the  urine.  Its  origin  is  easily  explained,  not  only  by  the  ingestion 
of  foods  which  contain  it  (sorrel,  tomatoes,  rhubarb),  but  in  addi- 
tion because  it  is  one  of  the  most  common  products  of  the  oxida- 
tion of  organic  substances.  In  fact,  the  oxidations,  in  the  organism 
as  well  as  in  the  alimentary  canal,  are  made  the  most  of  and  it  is 
only  gradually  and  through  intermediate  substances  that  we  arrive 
at  the  last  terms  of  the  oxidation  of  a  body. 

It  is  thus  that  uric  acid,  through  incomplete  oxidation,  gives 
rise  to  it  instead  of  being  reduced  into  urea  and  carbonic  acid. 
A  retardation  of  nutrition,  an  incomplete  hematosis,  favor  the 
production  of  oxalic  acid  ;  under  these  circumstances  the  inosite 
of  the  muscles  and  the  glycogen  of  the  liver  are  its  principal 
sources.  In  the  alimentary  canal  its  presence  and  its  formation 
have  hitherto  been  but  little  investigated. 

We  however  understand  that  it  may  result  from  the  incom- 
plete oxidation  of  starches  and  sugars,  as  well  as  from  reduction 
of  carbonic  anhydride  after  the  ingestion  of  beverages  which 
contain  it  (sparkling  wines,  beers,  etc).,  or  from  acid  carbonates. 
It  is  also  one  of  the  derivatives  of  leucin.  Bayard '  has  con- 
sidered it  as  the  product  of  certain  gastric  affections.  Very 
recently.  Dr.  Boursier"  (of  Contrexeville,  old  interne  of  the  Paris 
hospitals),  has  expressed  the  same  opinion. 

"  With  certain  patients,"  he  says,  "  oxalate  of  lime  appears 
to  be  constantly  eliminated  and  to  be  accompanied  by  certain 
symptoms  (dyspepsia,  nervous  disturbances),  which  seem  to  give 
rise  to  a  special  disease  :  oxaluria.      But  dyspepsia  is  one  of  the 

'  Bayard,  Traitd pratique  des  maladies  de  /'  estomac,  1872,  page  213. 
''A.  Boursier,  Ann.  de  la  Soc.  d'  hydrologie,  analyse  en  Journal  de  me'd.  et  decJdr, 
pratiques,  25  juin,  1884. 


Alimentary  Poisons.  17 

most  frequent  of  symptoms  Avith  oxalurics,  and  the  formation 
of  oxalates  would  seem  to  be  a  consequence  of  this  dyspepsia. 
Oxaluria  would  be  rather  a  symptom  of  a  form  of  dyspepsia  than  a 
distinct  disease." 

That  which  well  shows  that  there  is  here  an  auto-intoxication, 
a  chemical  impregnation,  is  that  there  are  in  these  cases  head- 
aches, disturbances  of  vision,  as  in  uraemia ;  the  skin  is  dry  and 
rough,  is  sometimes  covered  with  profuse  sweats  ;  boils  and  car- 
buncles are  frequent. 

Aldehydes. — The  aldehydes  are  the  first  products  of  the  oxi- 
dation of  the  alcohols ;  but  it  is  not  solely  as  derivatives  of  the 
alcohols  that  they  here  have  their  place. 

"■  In  a  celebrated  hypothesis,  Liebig  has  admitted  that  the 
organic  acids  once  formed  may  give  rise  to  aldehydes  by  a  fur- 
ther reduction  "  (Wurtz,  Chimie  biologigue).  On  the  other  hand, 
Guckelberger,'  by  oxidizing  albuminoid  matters,  has  obtained 
notable  proportions  of  ordinary,  propionic,  butyric,  and  benzoic 
aldehyde  (essence  of  bitter  almonds).  Now,  the  organic  acids 
are  formed  in  dilated  stomachs,  and  the  albuminoids  there  undergo 
every  species  of  transformation.  Supposing  that  the  aldehydes 
of  themselves  have  no  injurious  influence  (see  the  experimental 
portion),  they  obtain  one  by  the  property  which  they  have  of 
producing  an  acid  under  the  influence  of  the  agents  that  oxidize 
ordinary  alcohol : 

CgHgO  C2H4O  CgH^Og 

Ethylic  alcohol.         Ordinary  aldehyde.         Acetic  acid. 

Through  its  agency  we  again  find  acetic  acid.  In  fact,  the  pres- 
ence of  a  small  quantity  of  aldehyde  has  been  observed  in  vine- 
gar (GEchsner  de  Coninck).  In  alcoholic  fermentations  protected 
from  the  air,  the  alcohol  is  oxidized  into  the  state  of  aldehyde 
(Schutzenberger  and  Destrem) ;  the  fungus  of  muguet  transforms 
alcohol  into  aldehyde  (Linossier  and  G.  Roux) ;  lastly,  the  simple 
exposure  of  aldehyde  to  the  air  is  sufficient  to  transform  it  into 
acetic  acid. 

Acetones. — The  acetones  are  the  aldehydes  of  the  secondary 
alcohols.  We  know  that,  since  Markownikoff  has  observed  their 
presence  in  the  urine  of  diabetics,  to  acetone  is  attributable  the 
principal  role  in  diabetic  coma.     Stadelmann,  Kulz,  Minkowski, 

^  Guckelberger,  cMpar  CEchsner  de  Coninck,  Chimie  organique,  1892. 


1 8  The  Liver  of  Dyspeptics. 

and  Lepine  *  have  shown  that  acetone  is  only  the  last  term  of  the 
oxidation  of  /?  oxybutyric  and  diacetic  acids,  and  that  it  is  to  this 
acid  dyscrasia  that  it  is  proper  to  attribute  the  diabetic  coma. 

In  fact,  fi  oxybutyric  acid  is  a  superior  homologue  of  lac- 
tic acid,  and  on  this  account  is  probably  more  toxic.  Now, 
whence  come  these  acids  ?  They  arise  from  the  fermentation 
and  chemical  splitting  up  of  albuminoid  matters  under  the  influ- 
ence of  gradual  oxidations :  the  acetone  is  only  the  evidence  of 
these  complex  processes  leading  to  the  formation  of  intermediate 
toxic  products.  These  imperfect  transformations  of  the  albu- 
minoids do  not  take  place  solely  in  the  inmost  recesses  of  our 
tissues,  as  in  diabetes,  but  also  in  the  alimentary  canal. 

H.  Lorenz,*  assistant  of  Professor  Nothnagel,  has  carefully 
studied  the  acetonuria  and  diaceturia  of  digestive  origin.  As  early 
as  i860,  Kaulich  had  found  acetonuria  in  various  diseases  which 
had  digestive  disturbances  as  a  common  symptom,  and  had  rec- 
ognized the  fact  that  acetone  was  formed  in  the  gastro-intestinal 
tract.  Von  Jaksch  ^  has  again  found  it  in  a  goodly  number  of 
pathological  conditions,  particularly  in  dyspeptic  coma.  Lorenz 
has  very  carefully  investigated  this  subject ;  he  has  encountered 
acetonuria,  and  sometimes  diaceturia,  in  digestive  disturbances 
consecutive  to  the  ingestion  of  spoiled  meats ;  in  ulcer  and  dila- 
tation of  the  stomach,  in  chronic  gastro-enteritis,  but  more  espe- 
cially in  acute  cases. 

The  aggravation  of  the  symptoms  coincides  with  an  increase 
of  the  acetone  eliminated.  He  has  again  found  acetone,  but  with 
less  constancy,  in  the  neuroses  of  the  stomach,  the  gastric  crises 
of  tabes  ;  in  four  cases  of  hysteria  with  digestive  troubles  there 
was  acetone  in  the  urine  ;  in  two  of  them,  some  acetylacetic  acid  ; 
in  one,  some  ft  oxybutyric  acid.  Lorenz  regards  as  arising  from 
the  intoxication  produced  by  acetone,  or  by  other  substances  in- 
termediate between  the  albuminoids  and  this  body,  certain  symp- 
toms which  are  ordinarily  connected  with  digestive  disturbances  ; 
such  as  a  sensitiveness  of  the  epigastrium  and  spontaneous  pains 
(cramps)  in  the  region  of  the  stomach. 

He  believes  that  these  phenomena  arise  from  an  irritation  of 
the  coeliac  plexus,  the  extirpation  of  which  would  determine 
acetonuria,  according  to  Churton  and  Lustig. 

*  Lepine,  loc.  cit. 

*  Lorenz,  Zeitschr.  f.  klin.  Med.,  xix,  Bd. 

^  Von  Jaksch,  Zeitschr.  f.  klin.  Med.,  xi.  Bd. 


Alimentary  Poisons.  19 

On  the  other  hand,  functional  disturbances  of  the  coeliac 
plexus  lead  to  abnormal  fermentations,  and  may  also  produce 
acetonuria.  Lorenz  considers  the  alimentary  canal  as  the  place 
of  production  of  acetone  in  cases  of  digestive  acetonuria.  He 
has  found  this  substance  in  matters  from  the  stomach  and,  espe- 
cially from  the  intestine,  in  all  his  clinical  cases,  save  in  the  ner- 
vous affections  of  the  stomach. 

Other  Poisons. — We  besides  observe  in  the  stomach  the  pres- 
ence of  syntonin  or  acid  albumen  which,  if  it  is  not  ulteriorly 
transformed  into  peptones,  would  have  a  certain  toxicity.  All 
these  first  terms  of  the  digestion  of  albuminoids  are  yet  im- 
perfectly known,  especially  from  the  stand-point  of  their  nox- 
iousness. 

Let  us  not  forget  \.h.e  peptotoxin  of  Brieger.  Lastly,  if  we  pass 
to  the  intestine,  besides  the  bodies  already  mentioned,  we  will 
find  the  excretory  products  of  the  bile,  very  toxic  of  themselves 
(since  5  cubic  centimetres  of  ox  bile  kills  a  rabbit  weighing  1500 
grams),  and  which,  in  part,  are  absorbed  by  the  intestine:  ijidol, 
scatol,  cresol,  the  phenols,  the  excretin  of  Marcet,  the  salts  of 
Jfotash,  carbiiretted  dind  sulphuretted  hydrogen,  etc. 

M.  Bouchard  has  shown  in  an  exact  manner  the  toxicity  of 
the  intestinal  contents.  An  aqueous  and  especially  an  alcoholic 
extract  of  fsecal  matters  in  small  amounts  kills  various  animals. 

Micro-organisms. — The  various  products  above  enumerated 
result,  for  the  most  part,  from  the  action  of  micro-organisms,  fer- 
ments or  microbes,  contained  in  the  alimentary  canal.  They  are 
swallowed  with  the  food,  either  originally  contained  in  it  or 
mixed  with  it  in  its  passage  through  the  mouth:  a  large  number 
are  carried  into  the  stomach  with  the  swallowed  saliva.  Lastly, 
certain  species  normally  inhabit  the  stomach  and  especially  the 
intestine,  in  which  the  permanent  alkalinity  of  the  medium  favors 
their  multiplication.  To-day  we  no  longer  speak  of  the  anti- 
fermentative  property  of  the  bile.  Letienne  *  has  shown  that  its 
antiseptic  action  is  much  less  than  has  been  commonly  supposed.  . 
Certain  microbes,  such  as  the  Staphylococcus  aureus  and  the  Bacil- 
lus coli  communis,  &2iS\\y  \iyq  \n  pure  bile.  Certain  biles  are  also 
particularly  propitious  to  the  development  of  organisms. 

In  even  the  normal  stomach,  bacteriologists  have  discovered 
the  presence  of  numerous  species.     The  sarcina,  discovered  in 
1842  by  Goodsir,  and  since  that  time  thoroughly  investigated  by 
'  Letienne,  Thhe  de  Paris,  1891. 


20  The  Liver  of  Dyspeptics. 

Falkensheim,  has  no  peculiar  signification.  It  is  especially  plenti- 
ful in  dilated  and  cancerous  stomachs.  Some  cases  have  been 
cited,  says  Bouveret,  in  which  a  drop  of  gastric  liquid  was  as  rich 
in  sarcinae  as  a  drop  of  culture  liquid. 

De  Bary  has  found  several  fungi :  the  O'idium  albicans,  the 
Leptothrix  buccalis,  and  a  new  one  which  he  calls  Bacillus  genicu- 
latus.  Abelous '  has  counted  in  the  healthy  stomach  sixteen 
species  of  which  seven  are  known :  the  sarcina.  Bacillus  pyocy- 
aneus,  Bacillus  lactis  erythrogenes.  Bacillus  subtilis,  the  Vibria 
rugula,  Bacillus  amylobaeter,  Bacillus  megateriwn.  Capitan  and 
Moreau  "^  have  isolated  three  undetermined  types.  In  addition^ 
there  are  some  yeasts,  among  which  the  alcoholic  yeast.  Lastly, 
we  have  incidentally  observed  the  microbes  of  various  fermenta- 
tions. 

But,  in  diseased  stomachs  with  lessened  secretion,  the  Bacil- 
lus coli  cotmnunis  is,  according  to  Lesage,  the  most  frequent ;  its 
virulence  is  insignificant.  However,  two  Italian  experimenters, 
MM.  Cesaris-Demel  and  Orlandi,'  have  been  able  to  convince 
themselves  that  the  Bacillus  coli  acquires  great  virulence  by  its 
culture  in  gastric  juice,  to  such  an  extent  that  guinea-pigs,  ordi- 
narily little  sensitive  to  the  action  of  this  microbe,  succumb  con- 
sequent upon  an  injection  of  a  cubic  centimetre  of  this  liquid  into 
the  peritoneum. 

The  Bacillus  coli  is  an  especially  dangerous  guest  to  the 
intestine  ;  it  reigns  there  despotically ;  it  there  freely  multiplies 
and  it  borrows,  from  some  conditions  which  we  as  yet  very 
imperfectly  understand,  an  exaltation  of  its  virulence  more  or 
less  temporary  which  may  elevate  it  to  the  rank  of  a  pathogenic 
microbe.  Its  secretory  products,  even  when  it  appears  the  most 
inoffensive,  must  always  be  looked  upon  with  suspicion. 

The  list  of  pathological  acts  which  they  attribute  to  it  daily 
grows  longer,  and  its  history  becomes  more  complex  and  as 
sombre  as  that  of  many  a  nobler  microbe  whose  toxicity  is  fixed 
and  determined.  It  is  a  hardy  species  which  accommodates 
itself  as  well  to  the  presence  as  to  the  absence  of  oxygen  and 
gains  fresh  strength  by  its  association  with  other  microbes ;  it  is 
the  parasite  par  excellence,  as  well  of  man  as  of  the  lower  animals 
and  of  the  other  micro-organisms  themselves,  and  well  knows 

'  Abelous,  These  de  Montpellier,  1888. 

-  Capitan  et  Moreau,  Soc.  de  biologie,  1889. 

'  Cesaris-Demel  et  Orlandi,  Acad.  med.  de  Turin,  seance  du  28  Janvier,  1893. 


Alimentary  Poisons.  21 

how  to  turn  to  its  own  advantage  every  opportunity  of  injuring 
its  host.  For  its  natural  habits  and  pathological  role,  be  kind 
enough  to  refer  to  the  excellent  monograph  of  Macaigne,'  and  to 
the  various  articles  since  published  in  the  transactions  of  the 
biological  and  hospital  societies  by  different  authors,  among 
others,  by  my  preceptor,  M.  Hanot,^  and  by  myself/ 

Although  they  have  their  importance,  not  only  as  agents  of 
distension,  but  also  as  mediums  destitute  of  oxygen  and  therefore 
favorable  to  the  growth  of  the  majority  of  microbes,  I  shall  say 
nothing  in  regard  to  the  gases  of  fermetitation :  carbonic  acid, 
hydrogen,  and  sulphuretted  hydrogen.  In  the  diseased  stomachs 
of  alcoholics  and  of  those  individuals  suffering  from  dilatation  we 
frequently  find  bile  and  pancreatic  juice,  the  reflux  of  which  is 
rendered  easier  by  the  atony  of  the  pylorus  and  by  the  existence 
of  a  duodenal  alteration. 

Their  alkalinity  greatly  favors  the  secondary  fermentations 
and  the  production  of  organic  acids  ;  the  bile,  moreover,  contains 
the  excrementitious  matters  of  the  liver,  and  the  pancreatic  juice 
a  certain  quantity  of  fatty  acids.  We  have  just  read  something 
in  regard  to  the  present  opinion  in  reference  to  the  antiseptic 
qualities  of  the  bile.  Finally,  a  last  element  comes  to  the  aid  of 
the  fermentative  processes,  especially  in  the  stomach ;  I  refer  to 
mucus,  always  present  in  the  stomach  at  the  time  of  digestion, 
and  in  the  majority  of  gastric  diseases  permanently  present  and 
in  large  quantity.  It  was  formerly  believed  to  be  endowed  with 
saccharizing  properties,  and  of  itself  alone  capable  of  producing 
the  organic  acids  which  we  have  investigated ;  its  role  to-day, 
however,  has  devolved  upon  the  ferments  and  microbes.  It 
contents  itself,  and  this  is  sufficient,  with  furnishing  them  a 
medium  of  a  constant  alkalinity  which  protects  them  against  the 
action  of  the  hydrochloric  acid  contained  in  the  gastric  juice. 

Minkowski*  thus  sums  up  the  effects  of  the  gastric  fermen- 
tations: "  They  give  rise  to  products  of  a  nature  to  irritate  the 
mucous  membrane  and  there  provoke  a  catarrhal  condition  ;  they 
develop  gases,  sometimes  in  great  quantity,  are  a  cause  of  malaise 

'  M.  Macaigne,  Thhse  de  Paris,  1891. 

*  Hanot,  "  De  I'ictere  grave  hypothermique,"  Arch.  gen.  de  med.,  avril,  1893; 
"  Ictere  grave  colibacillaire,"  Soc.  de  biol.,  17  fevrier,  1894,  et  Soc.  med.  des  kdpi- 
taux,  4  mai,  1894. 

^  Boix,  "  De  Taction  hypothermisante  du  Bacillus  coli  com.,"  Mimoire  h  la  Soc. 
de  biologic,  27  mai,  1893,  et  8  juin,  1893. 

^  Minkowski,  Mittheil,  aus  der  med,  Klin,  zu  Konigsberg,  Leipzig,  1888. 


22  The  Liver  of  Dyspeptics. 

to  the  patient,  and  aggravate  the  gastric  atony.  Among  the  sub- 
stances produced,  certain  ones  exercise  a  toxic  influence  and  the 
fermentations  of  the  albuminoids  may  engender  bases  which 
neutraHze  the  hydrochloric  acid." 

It  was  not  irrelevant  to  pass  in  review,  at  least  in  a  summary 
manner,  the  poisons  of  the  alimentary  canal.  An  etiology  care- 
ful of  the  truth  must  justify  the  doctrine,  henceforth  sovereign, 
of  auto-intoxication,  and  not  take  up  the  subject  of  pathogeny 
with  insufficient  knowledge  of  the  causes  of  disease. 


CHAPTER  III. 

CONDITIONS   WHICH   FAVOR  THE   PRODUCTION   OF   THESE 

POISONS. 

It  is  now  fitting  that  we  should  analyze  the  conditions  under 
which  the  abnormal  fermentations  arise,  and  ascertain,  among  the 
diseases  of  the  stomach  or  intestine,  those  which  realize  these 
conditions.  Two  causes  play  the  principal  role :  motor  insuffi- 
ciency d^nd  stagnation  of  the  ingesta.  The  insufficiency  of  hydro- 
chloric acid  as  an  anti-zymotic  renders  the  diminution  of  the  secre- 
tion of  the  gastric  juice  less  important;  somewhat  less  important 
also  are  the  alterations  of  the  mucous  membrane. 

It  is  the  dilatation  of  the  stomach  which  we  must  especially 
consider.  M.  Bouchard  thus  defines  dilatation  :  "  Every  stomach 
which  does  not  contract  when  it  is  empty  is  a  dilated  stomach." 
This  definition,  absolutely  correct  from  an  anatomical  point  of 
view,  is  not  perhaps  sufficiently  comprehensive,  and  if  it  leaves  it 
to  be  understood  that  the  stomach  which  does  not  contract  con- 
tains a  chyme  imperfectly  elaborated  and  in  process  of  fermenta- 
tion, it  does  not  say  so. 

M.  Bouveret  is  more  explicit.  For  him,  dilatation  of  the 
stomach  is  "  a  permanent  pathological  condition  which  at  one  and 
the  same  time  is  characterized  by  increase  of  volume,  diminution 
of  tonicity,  and  existence  of  retention."  By  this  definition  the 
dilated  stomach  is  distinguished  from  the  large  and  from  the  in- 
sufficient stomach.  More  practical,  MM.  Debove  and  Remond 
define  dilatation  as  "an  insufficiency  of  motor  functions,  so  that 
this  organ  ordinarily  contains  in  the  morning,  when  the  patient  is 
fasting,  food  in  marked  quantity."  They  have  endeavored  to 
distinguish  dilatation  pushed  to  this  extreme  (in  a  physiological 
sense)  from  sitnple  distentio?i  and  atony.  Rosenbach  recognizes  a 
certain  degree  of  relaxation  which  he  calls  gastric  insufficiency. 
Boas  has  proposed  the  term  myasthenia.  In  these  cases  there  is 
a  more  or  less  marked  diminution  of  the  tonicity  and  elasticity^ 
of  the  muscular  tunic  ;  clapotage  (splashing)  can  be  readily  in- 

23 


24  The  Liver  of  Dyspeptics. 

duced  during  the  whole  or  the  greater  portion  of  the  digestive 
period ;  but,  be  the  stomach  small  or  large,  it  is  empty  in  the 
morning  or  only  contains  secretory  products,  mucus  or  gastric  juice. 

It  seems  to  me  that  it  is  not  particularly  important  to  differ- 
entiate in  words  the  degree  more  or  less  marked  of  the  stomachal 
dilatation  and  alimentary  stasis.  Where  does  atony  end  and 
dilatation  commence  ?  At  what  hour  must  the  stomach  be  com- 
pletely empty  in  order  that  we  may  decide  if  there  is  or  is  not 
stagnation  of  the  food  ? 

One  sentence  appears  to  me  capable  of  truthfully  expressing, 
from  the  stand-point  of  pathogenic  result,  the  condition  of  a 
stomach  the  motor  functions  of  which  are  defective,  and  I  would 
willingly  accept  this  definition,  if  it  is  one  ;  stomachal  dilatation  is 
a  constipation  of  the  stomach.  This  definition  comprehends  at  one 
and  the  same  time  :  asthenia  of  the  muscular  tunic,  the  alimen- 
tary stasis  which  follows  it,  and  the  abnormal  fermentations  which 
are  its  consequence. 

It  considers  the  word  dilatation  in  its  broadest  sense  and  es- 
tablishes a  connection,  too  frequently  neglected,  between  the 
condition  of  the  stomach  and  that  of  the  intestine.  It  is  a  mis- 
take, says  Lasegue,'  by  our  arbitrary  analysis  to  isolate  gastric 
from  intestinal  pathology.  These  two  portions  of  the  alimentary 
canal  are  conjointly  responsible  and  we  may  say  that  auto-intoxi- 
cation of  gastro-intestinal  origin  finds  its  sufficient  reason  in  consti- 
pation. Whatever  may  be  the  cause  of  it — pyloric  obstruction  of 
every  kind,  chronic  gastritis,  primitive  or  nervous  atony,  excess 
of  foods  or  drinks — stomachal  dilatation  with  stagnation  of  ingesta 
is,  the  same  as  intestinal  atony  with  coprostasis,  a  source  of  injuri- 
ous substances  so  much  the  more  easily  absorbed  as  the  stasis  is 
longer. 

M.  Bouchard  has  translated  this  into  clinical  language  as  fol- 
lows :  "  The  appetite  is  generally  preserved  ;  it  may  be  increased. 
The  majority  of  individuals  with  dilated  stomachs  eat  heartily. 
Ingestion  is  not  at  all  painful,  but  at  the  end  of  two,  three, 
or  four  hours  the  stomach  is  distended  ;  there  are  eructations  at 
first  inodorous,  then  sour,  sometimes /"^^/(//  a  sensation  of  weight, 
of  burning  in  the  epigastrium,  some  pyrosis,  regurgitations  of 
which  the  acid  odor  detnonstrates  the  reality  of  the  abnormal  fer- 
mentations which  are  taking  place  in  the  stomach,  for  hydro- 
chloric acid  has  no  sour  smell, — this  is  due  to  acetic  acid. 

'  Lasegue,  Introduction  au  Traite  des  maladies  de  I'estomac  de  Brinton,  1870. 


The  Production  of  these  Poisons.  25 

"The  faecal  matters  are  generally  pasty,  offensive,  acid;  al- 
though soft,  they  are  expelled  slowly  and  with  difificulty.  We 
can  assure  ourselves  of  the  fact  that  their  acidity  is  due  to  the 
predominance  of  acetic  acid.  The  consequence  of  this  develop- 
ment of  acid  along  the  whole  length  of  the  alimentary  canal  is  an 
inflammatory  condition.  We  observe  catarrh  of  the  stomach  and 
ulcerative  gastritis,  to  which  the  patients  may  succumb  after 
having  had  a  bad  stomach  for  twenty-five  years :  these  are  the  so- 
called  cases  of  false  cancer,  or  malignant  gastritis  without  tumor. 
The  large  intestine  is  inflamed  ;  glairy  secretions  surround  the 
faecal  matters,  sometimes  some  blood  is  present  (membranous 
enteritis)." ' 

To  the  dilatation  of  the  stomach,  properly  speaking,  after  a 
certain  time  is  added  chronic  gastritis  which  contributes,  through 
the  plentifulness  of  the  secreted  mucus,  to  the  production  of  ab- 
normal fermentations.  It  is  to  M.  Hayem  especially  that  is  due 
the  great  credit  of  having  shown  that  the  termination  of  the 
majority  of  the  inflammations  of  the  stomachal  mucous  membrane 
is  a  mucous  transformation  of  the  glands  of  the  stomach.  We 
know  that,  from  the  point  of  view  of  pathological  anatomy  as  well 
as  from  a  physiological  stand-point,  we  may  divide  the  cellular 
elements  into  two  apparatuses. 

The  first,  the  muco-pyloric,  comprehends :  first,  all  the  epithe- 
lium of  the  surface  which  furnishes  the  mucus  (caliciform  or 
goblet  cells)  ;  and  second,  the  principal  cells  of  the  pyloric  glands, 
which  do  not  fabricate  mucus  as  we  have  supposed,  but  of  which 
the  secretion  seems  devoid  of  digestive  properties,  although  con- 
taining some  ferments.  The  second  is  the  peptic  apparatus, 
comprehending  the  whole  of  the  glands  containing  both  the  chief 
and  parietal  cells. 

Now,  what  takes  place  in  the  majority  of  the  cases  of  gastritis 
either  immediately,  in  the  gastritis  termed  mucous  at  the  first 
onset  (d'emblee),  or  in  the  long  run  in  hyperpeptic  gastritis?  A 
mucous  transformation  of  the  glands  of  the  stomach.  The  surface 
epithelium  is  hypertrophied,  and  there  is  cellular  proHferation  of 
its  deep  layer.  At  the  bottom  of  the  funnel-shaped  tubes  of  the 
neck  of  the  glands,  some  cellular  buds  shoot  forth  which  pene- 
trate the  meshes  of  the  areolar  tissue.  From  these  buds  new 
glands  are  soon  formed  which  in  part  take  the  place  of  the  altered 
or  atrophied  peptic  glands,  so  that  it  is  a  new  mucous  membrane 

'  Bouchard,  loc.  cit.,  p.  171. 


26  The  Liver  of  Dyspeptics. 

which  has  replaced  the  old,  and,  physiologically,  there  results  from 
it  a  destruction  of  the  digestive  properties  of  the  gastric  juice 
(Hayem).'  This  anatomical  discovery  (and  it  is  manifest  upon 
the  preparations  of  M.  Hayem  which  I  have  had  the  honor  to 
examine  in  his  laboratory)  gives  a  clear  explanation  of  a  fact 
which  clinically  had  been  observed  for  a  long  time:  a  diminution 
of  digestive  functions  in  connection  with  a  very  large  quantity  of 
mucus.  "  To  a  first  stage  of  acid  catarrh,"  say  Debove  and  Re- 
mond,'*  "  (whatever  may  be  the  origin  of  the  gastritis),  succeeds 
little  by  little  a  diminution  of  the  hydrochloric  secretion  which  is 
replaced  by  a  neutral  or  alkaline  mucous  liquid,  still  rich  in  pep- 
sin ;  but  this  ferment  itself  soon  disappears,  and  the  gastric  con- 
tents are  no  longer  anything  but  a  mucus  turbid  from  white 
globules  and  desquamated  cells." 

These  authors  besides  say  that  chronic  gastritis  "  is  accom- 
panied by  a  hyperactivity  of  the  mucous  glands,  the  secretory 
products  of  which  cover  the  gastric  walls  with  a  glairy  coating." 
We  must  not  forget  that  chronic  gastritis,  under  whatever  ana- 
tomical form  it  presents  itself,  causes  an  alteration  of  the  muscular 
tunic, — atrophy  or  sclerosis.  It  would  be  useless  to  speak  in  detail 
of  the  diseases  of  the  stomach  in  which  abnormal  fermentations 
are  encountered.  It  would  be  necessary  to  study  them  all  one 
after  the  other,  since  all  terminate  in  atony  and  chronic  gastritis. 
Says  M.  Hayem,  even  the  so-called  nervous  dyspepsias  always 
commence  with  a  gastropathy.  I  will  confine  myself  to  quoting 
here  a  page  from  his  Clinical  Lectures:  "They  have  said  of 
nervous  dyspepsia  that  it  was  a  romance.  Alas,  no,  not  from  a 
semeiological  point  of  view.  No  description  of  distressing  symp- 
toms can  be  more  precise  than  that  given  us  by  those  suffering 
from  gastric  disease.  But  it  is  a  tower  of  Babel ;  it  is  the  chapter 
in  which,  besides  some  cases  with  which  I  shall  soon  acquaint 
you,  we  find  other  cases  illy  understood,  incorrectly  interpreted, 
incompletely  investigated  ;  I  might  almost  dare  to  say,  wrongly 
diagnosed.  Dyspepsia  is  the  semeiological  expression  of  the 
gastropaths  who  suffer.  It  may  even  be  solely  constituted  by 
remote  symptoms,  in  some  sort  extra-stomachal,  the  gastropathy 
proper  remaining  latent.  If  you  make  of  this  dyspepsia  a  pri- 
mary nervous  condition  upon  which  the  gastric  affection  depends, 
then,  contrarily  to  what  takes  place  with  other  organs,  all  the 

'  Hayem,  Bulletin  medical,  1894,  No.  6. 
'  Debove  et  Remond,  loc.  cit.,  p.  216. 


TJie  Prodticiion  of  these  Poisons.  27 

lesions  of  the  stomach  which  I  have  described  to  you,  all,  with- 
out exception,  are  secondary,  and  the  consequence  of  a  prinaary 
nervous  condition. 

"  We  must  make  a  choice :  gastropaths  are  neuropaths  or 
they  have  an  organo-pathic  affection.  The  true  relationship  of 
the  morbid  evolution  is  generally  not  recognized.  Sufficient 
attention  has  not  been  paid  to  the  true  cause  of  gastric  affections, 
to  the  good  nature  (bonhomie)  with  which  the  stomach  remains 
diseased  for  a  long  time  without  manifesting  in  a  perceptible 
manner  its  condition  of  organo-pathic  suffering.  We  ignore  these 
latent  gastric  conditions,  of  which  I  was  careful  to  speak  to  you 
at  the  very  beginning  of  your  studies,  and  we  only  recognize  the 
morbid  state  when  it  becomes  a  dyspeptic  condition.  We  com- 
monly say  that  the  dyspepsia  induces  the  organic  disease  of  the 
stomach.  Exactly  the  reverse  is  the  case:  the  organic  disease 
commences  first,  and  the  dyspepsia  follows.  Dyspepsia,  with  its 
sombre  cortege  of  nervous  phenomena,  is  one  of  the  consequences 
of  the  stomachal  alterations  with  which  I  have  made  you  familiar. 
It  is  far  from  being  the  only  danger  incurred  by  gastropaths,  and 
I  can  assure  you,  basing  my  opinion  upon  a  considerable  number 
of  clinical  cases,  that  the  gastropathies  open  the  door  for  a  great 
number  of  chronic  affections. 

"  Has  not  our  patient,  in  addition  to  his  nervous  troubles, 
incipient  renal  disease  and  a  bad  condition  of  the  liver?  In 
his  very  remarkable  work  upon  stomachal  dilatation,  my  col- 
league, M.  Bouchard,  mentions  some  cases  similar  to  those  which 
I  have  myself  observed,  and  I  am  happy  to  agree  with  him  in  re- 
gard to  this  point,  that  a  certain  number  of  individuals  with 
dilated  stomachs  are  not  yet  dyspeptic,  but  only  destined  to 
become  so. 

"  It  follows  from  my  special  studies  that  this  latent  dilatation 
is  the  consequence  of  a  developing  disturbance  of  digestion.  It 
is  only  the  second  link  of  a  chain  of  which  the  first  is  the  lesion  of 
the  stomach,  and  of  which  later  on  the  third  will  be  the  dyspepsia. 
People  do  not  have  dilated  stomachs  without  cause,  nor  suddenly. 
The  dilatation  indicates  a  condition  of  somewhat  long  standing. 
Examine  these  so-called  atonic  stomachs,  affected,  according  to 
the  theory,  with  motor  disturbances  of  nervous  origin  ;  you  will 
find  them  endowed  with  a  remarkable  contractility.  As  soon 
as  the  tube  enters  them  they  will  vigorously  eject  their  liquid 
contents.     We  may  even  say  that  they  are  sometimes  in  a  state 


28  The  Liver  of  Dyspeptics. 

of  motor  excitation.  True  atony,  stomachal  myasthenia,  is  rela- 
tively rare ;  it  is  one  of  the  remote  consequences  of  organic 
disease. 

"  To  recapitulate,  here  is  what  I  think  I  should  say  in  refer- 
ence to  clinical  observation:  we  frequently  come  into  the  world 
with  a  weak  stomach,  organically  little  fit  to  resist  the  numerous 
causes  of  irritation  which  assail  it.  If  I  had  to  treat  to-day  of  the 
etiology  of  the  gastropathies,  I  should  have  to  cite  to  you  many 
causes  which  would  explain  this  innate  weakness,  which  we  recog- 
nize for  many  other  organs  or  systems,  and  which  we  seem  to 
ignore  when  the  alimentary  canal  is  concerned. 

"  In  the  very  first  months  of  life,  gastro-intestinal  affections 
are  frequent  and  of  the  greatest  importance,  as  from  all  time  they 
have  been  the  principal  cause  of  infant  mortality.  Most  frequently 
our  patients  are  not  informed  in  regard  to  the  ailments  which 
they  have  had  during  this  epoch,  their  parents  either  not  having 
remembered  or  having  said  nothing  in  regard  to  them.  And, 
nevertheless,  these  first  injuries  of  a  mucous  membrane  yet  in 
process  of  development  may  be  sometimes  indelible.  Childhood 
comes  disturbed  by  acute  infectious  diseases,  producing  gastric 
disorders  and  frequently  becoming  the  occasion  of  an  inopportune 
medicinal  interference.  Without  enumerating  the  causes  of  gas- 
tritis, what  may  we  not  say  of  the  peculiar  diets  to  which  a  great 
number  of  children  are  subjected,  even  in  rich  families?  Do  you 
know  that  gastropathies  are  extremely  frequent  with  children  five 
and  six  years  old  ;  that  some  of  them  present  the  same  forms  of 
gastropathy  as  adults  ?  Very  soon  the  studies  commence  and  the 
influence  of  the  deplorable  school  hygiene.  An  alimentation 
vicious  and  coarse  or,  on  the  contrary,  in  certain  mediums,  too 
plentiful  and  too  nitrogenous,  insufficient  mastication,  work 
directly  after  or  a  little  time  after  meals,  the  body  bent  double  so 
as  to  make  the  liver  rest  upon  the  pylorus  or  duodenum,  the  con- 
finement in  an  impure  atmosphere,  the  lack  of  exercise — are  these 
facts  not  sufficient  to  explain  the  development  of  gastropathies  ? 
And  note,  moreover,  that  at  this  age  stomachal  affections  are  ap- 
parently rare.  The  child  is  puny,  poorly  developed,  but  it  does 
not  complain.  However,  you  will  find  that  it  has  already  a  dilated 
stomach  with  clapotage. 

"  We  reach  the  age  of  puberty  when  all  the  causes  of  gastric 
disease  are  going  to  be  accentuated.  At  this  epoch,  in  which  the 
organic  development  will  require  the  best  general  and  alimentary 


The  Production  of  these  Poisons.  29 

hygiene,  in  which  the  appetite  is  increased  in  proportion  to  the 
needs  of  the  economy,  they  set  to  work  to  prepare  themselves  for 
examinations,  they  abridge  the  time  devoted  to  recreations  and 
meals  ;  an  intellectual  effort  is  required  which  interferes  with  and 
interrupts  the  play  of  the  nutritive  functions. 

"  In  certain  mediums  the  vices  commence  to  produce  their 
fatal  effects  :  tobacco  and  alcohol  enter  upon  the  scene.  With  the 
young  girl,  we  must  take  the  corset  into  consideration,  which 
mechanically  impedes  the  gastric  evacuation.  Notice,  besides,  that 
these  different  causes  of  gastric  irritation  or  of  functional  annoy- 
ance are  frequently  present  with  individuals  predisposed  to  nerv- 
ous affections,  with  those  suffering  from  nervous  debility,  etc. : 
that  to  these  causes  is  added  cerebral  overwork,  which  we  must 
consider  in  order  to  comprehend  the  form  under  which  the 
stomachal  affection  is  going  to  present  itself.  It  is,  in  fact,  fre- 
quently at  puberty  or  a  little  after  that  the  gastropathy  mani- 
fests itself  outwardly,  so  to  speak,  and  frequently  also  its  first 
manifestation  will  be  in  the  form  of  a  dyspeptic  neurasthenia. 
The  clinical  form  of  the  disease  is  then  going  to  depend,  not 
solely  upon  the  lesion  of  the  stomach,  but  upon  the  individ- 
ual, upon  his  morbid  pre-dispositions,  upon  his  own  mode  of 
reaction.  Various  causes  acting  upon  the  stomach  will  have 
already  produced  the  gastropathy;  he,  the  patient,  will  create 
his  dyspepsia  in  his  own  way  by  imprinting  upon  it  his  indi- 
vidual seal,"  * 

After  this  long  and  suggestive  quotation,  any  digression  in  re- 
gard to  dyspepsias  of  long  standing  would  be,  it  seems  to  me, 
superfluous.  Dyspepsia  is  a  syndrome^  and  it  is  in  the  profound 
study  of  the  patient  and  of  his  alimentary  canal  that  we  shall  be 
able  to  unveil  the  true  cause  of  the  disease,  while  remembering 
however  these  two  aphorisms  of  MM.  Debove  and  Remond^: 
"  There  is  no  constant  relation  between  the  disturbances  of  the 
functions  of  the  stomach  and  the  sensations  of  the  patient." 
"  There  is  no  constant  relation  between  the  cause  and  the  form  of 
the  dyspepsia." 

Independent  of  dyspepsia  and  gastritis,  the  forms  of  which 
lend  themselves  a  little  to  the  interpretations  of  each  author, 
there  are  three  well  defined  morbid  types  :  acute  gastric  catarrh, 
(embarras  gastrique),  ulcer  of  the  stomach,  cancer  of  the  stomach. 

^  Hayem,  Bulletin  medical^  1894,  No.  31. 
*  Debove  et  Remond,  loc.  cit.,  p.  i6g. 


30  The  Liver  of  Dyspeptics. 

The  autopsies  of  Laboulbene,'  of  Ziegler,'  of  Sachs,"  etc.,  have 
proven  that,  at  the  very  commencement,  the  proportion  of  mucus 
increases  in  gastric  catarrh,  the  muciparous  glands  being  swol- 
len. At  the  same  time,  the  gastric  secretion  is  arrested  and 
the  acids  of  fermentation  are  formed,  whilst  the  micro-organisms 
multiply.  Ewald,  examining  the  matters  vomited  by  himself  and 
also  those  vomited  by  several  of  his  patients  while  suffering  from 
acute  gastric  catarrh,  has  found  that  the  filtered  liquid,  devoid  of 
hydrochloric  acid,  contained  traces  of  lactic  acid  and  quite  an 
amount  of  fatty  acids. 

Senator,  in  a  case  of  gastric  catarrh  of  two  days'  duration,  ob- 
served the  presence  of  sulphuretted  hydrogen  in  the  urine.  We 
think  that  the  repetition  of  accidents  of  this  kind  produces  a  posi- 
tive lesion  of  the  mucous  membrane  and  a  permanent  dilatation 
of  the  stomach.  In  ulcer  of  the  stomach,  the  mucous  membrane, 
even  remote  from  the  ulcer,  is  rarely  intact ;  we  ordinarily  find 
some  chronic  gastritis  or,  as  M.  Hayem  says,  some  hyperpeptic 
parenchymatous  gastritis,  and  as  in  Reichmann's  disease,  a  habit- 
ual hyperchlorhydria. 

These  patients  are  then  exposed  to  the  same  phenomena  of 
dilatation  and  stasis  as  the  preceding  ones.  In  cancer  of  the  stomach, 
we  find  gastric  dilatation  and  the  abnormal  fermentations  with  ab- 
sence of  HCl  in  almost  all  the  cases.  These  phenomena  are  at 
their  maximum  in  cancer  of  the  pylorus ;  besides  there  is  always 
a  co-existing  gastritis,  acute  or  chronic,  catarrhal  and  interstitial 
(Rosenheim,  Mathieu).*  Boas^  makes  the  presence  of  an  excess 
of  lactic  acid  in  the  stomachal  liquid,  after  the  test  meal,  a  sign  of 
gastric  cancer.  The  ulceration  of  the  tumor  is  a  gate  of  entry  for  the 
microbes  and  the  stomachal  toxic  products.  M,  Hanot  ^  has  called  . 
attention  to  the  septic(2mic  form  of  cancer  of  the  stomach  with  con- 
siderable painful  swelling  of  the  liver.  Lastly,  the  fever  of  cancer- 
ous patients,  due  perhaps  to  the  toxic  substances  produced  by  the 
neoplasm  itself,  may  also  be  attributed  to  the  absorption  of  gastro- 
intestinal poisons  proceeding  from  abnormal  fermentations. 

In  order  to  finish  this  chapter,  there  yet  remains  a  word  to  say 
in  regard  to  the  condition  of  the  stomach  in  certain  diseases. 

'  Laboulbene,  Anat.  path.,  1879. 

^Ziegler,  Allgtm.  und.  spec.  path.  Anat.,  1891. 

^  Sachs,  Inaug.  Dissertation,  Breslau,  1886. 

^  Mathieu,  Arch.  ghz.  de  m/decine,  1889. 

^Boas,  Deutsch.  med.   Wuchenschr,,  1892,  No,  17. 

®  Hanot,  Arch.  g/n.  de  m^decine,  1892. 


The  Produclio7t  of  these  Poisons.  31- 

Pulmonary  tuberculosis  is  accompanied,  especially  in  the  latter 
part  of  the  disease,  by  chronic  gastritis  with  or  without  anayloid 
degeneration,  Marfan  *  has  observed  this  gastritis  in  eighteen  out 
of  twenty-seven  tuberculous  patients.  It  is  probably  of  infectious 
origin. 

The  swallowed  expectoration  contains  not  only  the  tubercle 
bacillus,  but,  in  addition,  the  microbes  of  suppuration  and  various 
irritant  matters.  Their  injurious  action  upon  the  gastric  mucous 
membrane  is  so  much  the  greater  as  the  nutrition  is  disturbed  by 
the  fever  and  general  infection  of  the  organism. 

Typhoid  fever  h^s  also  some  gastric  accidents"  here  compre- 
hending dilatation,  which  likewise  may  precede  and  pave  the  way 
for  this  disease  (Bouchard).^  The  stomachs  of  diabetics  are  not 
indemnified  against  lesions.  Several  authors,  Cantani*  in  particu- 
lar, have  observed  interstitial  gastritis  with  glandular  atrophy. 
It  is  probable  that  this  condition  of  the  stomach  is  connected  with 
the  development  of  the  diabetic  cachexia.  We  are  also  familiar 
with  the  digestive  disturbances  of  individuals  suffering  from  heart 
disease.  It  is  the  common  chronic  gastritis  which  we  encounter 
most  frequently.  Lancereaux^  has  shown  that  there  is  a  venous 
hyperaemia  of  the  coats  of  the  stomach.  More  recently  Haute- 
coeur*  has  investigated  the  alteration  of  the  stomachal  chemism 
in  the  clinical  forms  of  the  cardiac  gastropathies. 

The  secretion  is  generally  diminished,  the  total  acidity  is  slight, 
the  proportions  of  free  and  combined  HCl  are  very  much  below 
the  normal,  and  if  the  total  acidity  is  great,  it  is  due,  in  great  part, 
to  the  acids  of  fermentation.  The  repeated  purgatives  which  they 
administer  to  those  suffering  from  asystolia,  particularly  drastic 
cathartics  like  the  German  eau  de  vie,  may  contribute  to  the  de- 
velopment of  gastric  catarrh.  How  many  patients  affected  with 
gastro-intestinal  urcBinia,  especially  the  slow  form  ''  are  considered 
and  treated  as  dyspeptics  !  Patients  with  Bright's  disease,  whose 
kidneys  function  badly,  force  their  stomachs  to  perform  a  vicari- 
ous function.     Pilliet^  has  shown  that  the  lesions  of  uraemic  gas- 

^  Marfan,  These  de  Paris,  1887. 

*  Chauffard,  These  de  Paris,  1882. 
^  Bouchard,  These  citde. 

^Cantani,  Le  diabete  sucre,  trad,  de  Charvet,  Paris,  1876. 
^  Lancereaux,  Atlas  d'anat.  pathol. 

*  Hautecoeur,  These  de  Paris,  1891. 
'  Pougis,   These  de  Paris,  1S77. 

*  Pilliet,  Soc.  de  biologie,  1887. 


32  The  Liver  of  Dysyeptics. 

tritis  are  no  other,  histologically,  than  those  of  common  chronic 
gastritis.  Lastly,  various  chronic  intoxications,  such  as  morphino- 
mania  (Hitzig),'  markedly  diminish  the  secretion  of  gastric  juice 
which  is  very  poor  in  HCl.  By  this  rapid  expose,  we  may  see 
how  frequent  are  the  cases  in  which  are  combined  the  three 
principal  factors  of  auto-intoxication  :  gastric  atony,  alimentary 
stasis,  chronic  gastritis.  The  state  of  the  intestine  in  the  various 
affections  of  this  organ  and  in  the  course  of  the  diseases  of  which 
we  have  just  spoken,  particularly  in  cancer  of  the  stomach  and  in 
tuberculosis,  would  show  us  that  this  portion  of  the  ahmentary 
canal  is  not  the  least  important  from  the  point  of  view  of  the  pro- 
duction of  toxic  matters  and  of  their  absorption.  To  undertake 
this  study  would  only  be  a  repetition. 

1  Hitzig,  Berl.  Gesellsch.  f.  Psych,  u.  Nervenkr.     Nov.,  1872. 


PART  II. 

The  Liver  of  Dyspeptics. 


CHAPTER  I. 

THE   LIVER  AND   ITS   POISONS. 

Stich  was  astonished,  says  M.  Bouchard,  at  the  fact  that  there 
were  so  many  poisons  in  the  alimentary  canal,  and  so  few  toxic 
accidents.  We  ourselves  are  less  surprised,  as  now,  besides  the 
eliminative  action  of  the  kidneys,  we  are  acquainted  with  that 
wonderful  function  of  the  liver  by  means  of  which  the  organism 
wards  off  the  assaults  of  poisons  of  every  kind,  whether  intro- 
duced from  without  or  elaborated  in  the  human  economy  itself. 

Although  in  1873,  Heger^  announced  the  fact  that  the  liver 
retains  a  portion  of  the  vegetable  alkaloids  which  traverse  it,  it  is 
to  Schiff  '  that  is  due  the  honor  of  having  first  carefully  studied 
this  property  of  the  hepatic  gland  ;  and  this  discovery,  as  remark- 
able as  that  of  glycogenesis,  places  its  author  by  the  side  of 
Claude  Bernard  in  the  history  of  the  physiology  of  the  liver. 

Since  that  time  numerous  authors  have  thoroughly  investi- 
gated this  question.  M.  Bouchard  has  greatly  contributed  to  its 
progress,  and  the  very  important  thesis  of  his  pupil,  G.  H.  Roger,' 
has  markedly  increased  our  knowledge  in  reference  to  this  import- 
ant physiological  point. 

For  a  long  time  we  had  known  that  the  liver  renders  certain 
substances  suitable  for  the  nutrition  of  our  cells,  which  would  not 
have  been  available  for  that  purpose  if  they  had  not  first  under- 
gone a  metamorphosis. 

"  Situated,  as  it  were,  at  the  principal  entrance  of  the  human 
economy,"  says  Blondlot,*  "  the  gate  through  which  must  pass 

^  Heger,  These  d' agr/gation,  Bruxelles,  1873. 
^  Schiff,  Arch,  des  sciences phys.  et  naturelles,  Geneve,  1877. 
^  G.  H.  Roger,  "  Action  du  foie  sur  les  poisons,"  Thkse  de  Paris.,  1887. 
*  Blondlot,  Essai  sur  les  fonctions  du  foie  et  de  ses  annexes,  Paris,  1846. 
^  33 


34  The  Liver  of  Dyspeptics. 

all  the  nutritious  substances  arriving  from  without  through  the 
portal  vein,  the  liver  arrests  their  progress,  in  order  to  make  them 
undergo  a  radical  decomposition."  But,  if  any  noxious  substances 
demand  admittance,  the  hepatic  cell,  by  virtue  of  a  sort  of  selec- 
tion reserved  for  its  protoplasm,  retains  or  transforms  them  : 
either  in  order  to  return  them  gradually  to  the  circulation  in 
harmless  amounts  or  in  forms  less  toxic,  thus  reaching  the  renal 
filter  which  eliminates  them  ;  or  they  are  removed  by  the  biliary 
vessels,  most  generally  after  they  have  been  converted  into  sub- 
stances less  easily  absorbed  by  the  intestine. 

This  protective  role  is  comparable  to  that  played  by  the  white 
blood  globules  with  other  injurious  substances.  We  may  say  that 
the  hepatic  cells  are  to  poisons  that  which  the  leucocytes  are  to 
micro-organisms  and  other  foreign  microscopic  bodies.  Their 
function,  in  regard  to  these  poisons,  is  a  sort  of  chemical  phago- 
cytosis. The  importance  of  the  hepatic  gland  was  well  under- 
stood by  Galen,  who  considered  the  liver  as  the  central  organ  of 
life.  '*  This  vast  conception,"  says  Poucel,'  from  every  stand-point 
appears  to  be  so  true  that,  in  my  opinion,  the  liver  is  to  vegetative 
life  that  which  the  brain  is  to  the  life  of  relation." 

However  this  place  of  honor  is  dangerous,  and  the  liver  may 
profoundly  suffer  from  the  attacks  of  the  noxious  substances, 
against  which  it  is  its  duty  to  protect  the  organism.  It  may  be 
found  unequal  to  its  task,  as  the  poisons  which  traverse  it  may  be 
in  too  great  quantity,  or  the  organ  itself  may  be  affected  with  a 
congenital  or  acquired  inferiority.  Again,  we  must  distinguish  in 
the  liver,  from  the  point  of  view  of  susceptibihty,  the  various 
parts  which  compose  it.  The  hepatic  cell  may  function  perfectly 
and  render  harmless  many  a  substance  which  will  exercise  an  irri- 
tant action  upon  the  portal  vessels  ;  in  other  cases,  a  poison  will 
arrive  at  the  liver  in  such  quantities  that  the  cell  will  be  destroyed 
before  the  different  passages  have  had  time  to  undergo  any 
appreciable  alteration. 

The  aphorism  of  Stahl,  vena  porta,  porta  malorum,  does  not 
apply  solely  to  the  economy  in  general ;  it  is  also  true  for  the 
liver  itself.  The  liver  may  be  affected  in  other  ways  than  by 
means  of  the  portal  vein :  through  the  hepatic  artery  it  partici- 
pates in  all  the  dyscrasias,  in  all  the  sanguineous  infections — 
septicaemias,  bacillsemias,  etc. ;    through   the   ductus    communis 

'  Poucel,  Z?^  Vinjluence  de  la  congestion  chron.  du  foie  dans  la  genlse  des  maladies, 
Maxseille,  1883,  p.  9. 


Hepatic  Congestion.  35 

choledochus,  inflammation  of  the  duodenum  can  easily  extend 
to  the  bihary  passages,  and  micro-organisms  readily  ascend  as 
far  as  the  canaliculi,  if  they  are  favored  by  the  least  retardation 
of  the  current  of  bile. 

Nevertheless,  the  portal  vein  is  the  channel  most  open  to  nox- 
ious influences  and  also  the  most  dangerous,  because  poisons  thus 
arriving  may  act  at  the  same  time  upon  the  three  constituent 
portions  of  the  hepatic  organ :  first  upon  the  portal  vein  itself, 
extra  and  intra-glandular ;  second  upon  the  hepatic  cells ;  third 
upon  the  excretory  passages,  the  canaliculi  and  the  biliary  canals. 
In  fact,  a  poisonous  substance  carried  into  the  stomach  or  intes- 
tine may  provoke  an  intra-  and  extra-hepatic  pylephlebitis.  Once 
the  poison  is  in  presence  of  the  hepatic  cells,  one  of  three  things 
may  happen  :  either  the  functioning  of  these  cells  will  be  normal 
and  adequate  to  destroy  or  transform  the  poison,  the  whole  evil 
being  arrested  in  the  afferent  portal  vessels ;  or  their  functioning 
will  be  inadequate,  and  then,  if  the  amount  of  poison  is  very 
great,  the  cells  will  succumb  ;  If  the  amount  is  not  so  large,  in- 
sufficient to  immediately  alter  the  cells,  they  will  be  able  to 
transform  a  portion  of  the  poison,  but  the  remaining  portion  may 
pursue  two  different  paths  :  first,  that  of  the  intra-lobular  veins, 
and  there  will  be,  independent  of  the  bi-venous  sclerosis,  a  slow 
intoxication  of  the  whole  economy  ;  second,  that  of  the  biliary 
canaliculi,  which  will  convey  the  poison  outwardly  but  not  with- 
out injury  to  themselves  as,  like  the  afferent  vessels,  they  will 
experience  its  irritative  effects. 

The  angio-cholitis  may  be  even  more  extensive  than  the  peri- 
phlebitis and,  in  addition,  there  may  be  a  new  formation  of  biliary 
canaliculi.  All  this,  certain  chemical  poisons  can  accomplish  as 
well  as  microbian  toxins.  Things  may  not  go  so  far,  especially  at 
the  commencement  of  the  affection,  and  we  witness  a  simple 
congestion  of  the  liver  of  greater  or  less  duration  ;  sometimes, 
however,  it  may  be  permanent. 


CHAPTER   II. 

CONGESTION   OF   THE   LIVER   OF    GASTRO-INTESTINAL   ORIGIN. 

The  relations  between  diseased  conditions  of  the  alimentary- 
canal  and  congestion  of  the  liver,  long  ago  attracted  the  attention 
of  physicians,  who  had  observed  an  increase  of  the  volume  of  this 
organ  with  dyspeptics,  employing  the  word  dyspepsia  in  its  broad- 
est sense.  Portal  ^  says  that  great  eaters  ordinarily  have  an  en- 
larged liver.  Casimir  Broussais,"  fils,  while  studying  chronic  duo- 
denitis, clearly  observed  the  effect  of  this  disease  upon  the  liver. 

"  By  the  touch,"  he  says,  "  we  can  distinguish  a  certain  swell- 
ing, the  seat  of  which  it  is  impossible  to  precisely  determine, 
from  the  normal  resistance  of  this  region  (duodenal).  This  tume- 
faction increases,  is  very  soon  visible,  and  by  palpation  we  can 
ascertain  that  the  anterior  border  of  the  liver  extends  beyond  the 
false  ribs.  There  is  evident  obstruction  of  this  organ.  The  tume- 
faction remains  and  may  make  such  progress  that  the  liver 
descends  as  far  as  the  umbilicus  and  even  sometimes  to  the  crest 
of  the  ilium." 

At  the  present  time  we  are  far  from  interpreting  things  in  the 
same  manner  as  did  the  elder  and  younger  Broussais,  or  from  in- 
voking, in  order  to  understand  the  relations  of  duodenitis  and 
congestion  of  the  liver,  the  famous  law  of  Bichat :  "  The  action 
of  glands  corresponds  to  the  stimulation  of  the  surfaces  where 
their  excretory  canals  end." 

For  a  long  period,  the  authors  of  works  upon  dyspepsia  or 
diseases  of  the  stomach  paid  no  attention  to  the  condition  of  the 
hepatic  gland.  We  can  convince  ourselves  of  this  fact  by  reading 
Cullen,  Barras,  Chomel,  Trousseau,  Beau,  Guipon,  Nonat,  Bayard, 
Brinton ;  G.  See,  Gubler,  and  Raymond  also  only  speak  of  the 
liver  in  order  to  point  out  the  effect  of  its  diseases  upon  the 
stomach.  We  must,  however,  make  an  exception  in  favor  of 
Andral. 

'  Portal,  Observations  sur  la  nature  et  le  traitement  des  maladies  du  foie^  1813. 
*  C.  Broussais,  These  de  Paris,  1825,  page  27. 

36 


Hepatic  Congestion.  37 

As  a  scrupulous  observer,  in  an  autopsy  he  would  not  pass  by 
any  microscopic  detail,  and  in  two  cases  of  ataxo-dynamic  fever, 
with  gastro-intestinal  lesions,  he  noted  that  "  the  liver  had  a  pink 
color  and  a  remarkable  thickness."  "  But,"  says  he,  "  this  lesion 
was  purely  accidental  and  very  probably  had  no  connection  with 
the  disease  from  which  the  patients  succumbed."  ' 

He  becomes  more  interesting  in  the  second  volume  and  asks 
the  question,"  "  If  a  great  number  of  diseases  of  the  liver  do  not  re- 
cognize for  their  cause,  for  their  point  of  departure,  a  gastro-intes- 
tinal affection.  An  observation  of  the  symptoms  leads  us  in  this 
respect  to  share  the  opinion  of  M.  Broussais,  who  admits  that,  in 
a  majority  of  cases  of  phlegmasia  of  the  liver,  there  is  duodenitis 
in  the  first  place. 

"  An  examination  of  the  causes,  under  the  influence  of  which 
chronic  hepatitis  is  quite  frequently  developed,  would  beside  lead 
us  to  place  its  point  of  departure  in  the  alimentary  canal.  In  fact, 
it  is  the  result  of  our  observations,  that  the  majority  of  individu- 
als who  have  died  of  chronic  hepatitis  have  used  alcoholic  liquors 
to  excess.  We  easily  comprehend  how  the  habitual  stimulation 
of  the  digestive  mucous  membrane  by  these  beverages,  through 
continuity  of  tissue,  was  extended  to  the  mucous  membrane  of 
the  excretory  canals  of  the  bile  and  from  thence  to  the  hepatic 
parenchyma.  Besides  it  has  been  experimentally  demonstrated 
that  alcohol  introduced  into  the  digestive  passages  of  an  animal 
is  there  rapidly  absorbed. 

"  Now,  borne  directly  into  the  liver  by  the  mesenteric  veins, 
cannot  the  alcoholic  molecules  there  directly  cause  an  intense  ir- 
ritation of  this  organ  ?  Lastly,  it  is  possible  that,  under  certain 
circumstances,  the  irritation  is  propagated  from  the  intestines  to 
the  liver  through  the  means  of  a  venous  inflammation.  This  is 
the  opinion  of  M.  Ribes.  We  know  that  careful  dissections  have 
informed  this  learned  anatomist  that  erysipelas  is  frequently  ac- 
companied by  a  phlegmasia  of  the  veins  ;  and,  from  this  he  thinks 
that  it  would  not  be  impossible  that,  in  certain  gastro-intestinal 
inflammations,  the  veins  which  originate  at  the  surface  of  the 
mucous  membrane  should  become  inflamed  ;  that  this  inflamma- 
tion should  spread  from  the  small  mesenteric  veins  to  the  trunk 
of  the  portal  vein  and  be  thus  extended  to  the  parenchyma  of 
the  liver." 

^  G.  Andral,  Clinique medicale ,  3  edit.,  t.  i.  Maladies  de  V abdomen,  t.  i. ,  observa- 
tions vi.  et  xvi. ,  p.  612,  1834.  "'  Ibidem,  t.  ii.,  p.  305  et  suivantes. 


38  The  Liver  of  Dyspeptics. 

Two  clinical  cases  follow :  one  of  an  individual  who  died  of 
gastro-enteritis,  the  post-mortem  examination  revealing  a  punct- 
ated injection  of  the  gastric  mucous  membrane,  and  of  the  lower 
third  of  the  ilium  and  caecum ;  there  was  also  an  intense  redness 
of  the  internal  surface  of  the  inferior  mesenteric  vein,  of  the 
trunk  of  the  portal  vein,  and  of  all  its  hepatic  ramifications.  The 
liver  itself  was  large,  very  red,  engorged  with  blood,  and  friable. 
The  other  case  was  that  of  a  subject  who  died  of  cancer  of  the 
pericardium,  in  which  there  was  a  red  induration  of  the  liver,  its 
veins  being  a  bright-red  color  on  their  internal  surface,  and,  in  the 
alimentary  canal,  there  were  signs  of  a  chronic  phlegmasia,  such 
as  a  mammillated  appearance  and  a  brownish  color  of  the  gastric 
mucous  membrane.  The  duodenum  was  of  the  same  color,  with 
some  ulcerations  and  a  remarkable  development  of  the  follicles, 
with  a  black  coloration  around  them  towards  the  end  of  the  small 
intestine,  in  the  caecum,  and  the  commencement  of  the  colon. 
Andral  remarks  in  regard  to  the  latter  case,  "  that  the  disease 
commenced  with  a  diarrhoea  which  appeared  to  be  the  only  affec- 
tion for  at  least  a  year.  It  was  only  at  the  end  of  this  period  that 
some  pain  was  felt  in  the  right  hypochondrium.  The  patient 
twice  had  jaundice,  and  later  on  ascites  finally  developed  itself. 
This  succession  of  symptoms  at  least  indicates  that  the  disease  of 
the  liver  was  consecutive  to  that  of  the  intestine." 

Here,  very  clearly  presented,  is  a  very  contemporaneous  patho- 
geny. In  the  same  volume,  Andral  gives  a  very  interesting  case,, 
questionable,  I  must  confess,  as  to  the  nature  of  the  hepatic  affec- 
tion, but  which  we  may  present  as  a  type  of  chronic  congestion  of 
the  liver,  consecutive  to  some  undeniable  gastro-intestinal  lesions. 
Andral  simply  calls  it  a  case  of  general  hypertrophy  of  the  liver 
with  chronic  gastro-duodenitis ;  no  jaundice. 

Case  i  (Andral).  ^ 

A  compositor,  aged  forty-three  years,  enters  Charity  Hospital 
in  the  following  condition  :  great  emaciation  ;  face  pallid  ;  copper- 
colored  spots  upon  the  skin  of  the  thorax,  back,  and  limbs.  The 
sharp  edge  of  the  liver  can  be  felt  in  a  very  distinct  manner  a 
little  below  the  level  of  the  umbilicus,  and  extends  to  the  left  of 
it  about  two  or  three  finger-breadths.  In  all  the  space  included 
within  two  supposed  extended  straight  lines,  one  reaching  from 
the  cartilaginous  border  of  the  false  ribs  on  the  left  side  to  a  little 

'  Andral,  loc.  cit.,  tome  ii.,  p.  374. 


Hepatic  Congestion.  39 

below  the  umbilicus  and  the  other  extending  from  this  latter 
point  to  the  right  flank,  we  feel  a  hard  body  with  smooth  surface, 
which  is  terminated  inferiorily  by  the  sharp  edge  mentioned 
above,  the  limits  of  which  to  the  left  cannot  be  exactly  indicated, 
and  which  above  appears  to  be  continued  behind  the  ribs.  There 
is  no  question  that  this  body  is  the  hypertrophied  liver. 

The  tumor  which  it  formed  was  completely  indolent.  But 
when  the  patient  ate  anything  or  drank  any  undiluted  wine,  he 
felt  a  painful  sensation  at  the  epigastrium,  which  sometimes  was 
only  temporary,  and  sometimes  was  prolonged  for  several  hours. 
The  tongue  had  its  natural  appearance,  save  that  it  was  somewhat 
paler  than  usual.  There  was  habitual  loss  of  appetite,  without 
increase  of  thirst,  without  nausea  or  vomiting.  The  stools  were 
infrequent,  the  faecal  matters  being  hard  and  brown  ;  the  urine 
scanty,  red,  and  full  of  sediment. 

The  pulse  was  ordinarily  rapid,  without  there  being  any  heat 
of  the  skin.  The  patient  tells  us  that,  six  years  before  his  en- 
trance into  the  hospital,  he  had  taken  a  great  deal  of  Van  Swie- 
ten's  solution  and  a  large  amount  of  a  decoction  of  sarsaparilla ; 
that  these  remedies  not  relieving  him  of  the  large  and  indolent 
buboes  which  he  had  in  his  groin,  as  the  result  of  the  chancre 
on  his  penis,  he  had  taken  a  certain  amount  of  sulphuric  acid 
united  with  cream  of  tartar.  But,  after  several  days'  employment 
of  this  remedy,  he  was  suddenly  taken  with  a  severe  pain,  tearing, 
in  his  epigastrium,  the  appearance  of  which  was  accompanied  by 
a  temporary  loss  of  consciousness  and  epileptiform  convulsive 
movements.  During  the  five  days  following  the  patient  kept  his. 
bed ;  the  epigastric  pain  gradually  lost  its  first  severity ;  but, 
dating  from  this  epoch,  his  digestion  was  difificult  and  painful, 
his  appetite  was  lost,  his  strength  and  flesh  have  gradually  grown 
less. 

The  patient  had  not  perceived  the  presence  of  the  tumor 
formed  by  the  liver,  which  is  not  astonishing,  as  it  formed  no 
projection  of  the  abdominal  walls  and  was  not  painful.  This  indi- 
vidual lived  nearly  six  weeks  after  his  entrance  into  the  hospital. 
During  this  time  we  saw  him  gradually  grow  thinner  and  weaker. 
Properly  speaking  there  never  was  any  fever.  During  the  last  ten 
days  of  his  life,  he  vomited  at  four  different  intervals  a  large 
amount  of  a  black  matter  resembling  coffee-grounds  :  thenceforth, 
alteration  more  and  more  profound  of  the  features  of  the  face, 
chilliness  of  the  extremities,  drowsiness,  and  death. 


40  The  Liver  of  Dyspeptics. 

A  utopsy. 

The  abdominal  walls  having  been  raised,  the  first  object  which 
struck  us  was  the  enormous  volume  which  the  liver  had  acquired. 
It  covered  a  large  portion  of  the  intestines,  extended  downwards 
to  a  little  above  the  crest  of  the  ilium,  and  reached  a  good  deal 
beyond  the  linea  alba.  Its  volume  relatively  to  that  of  the  other 
organs  was  similar  to  that  which  we  observe  with  the  foetus.  Its 
external  surface  showed  the  two  natural  substances  of  the  liver  very 
clearly.  In  the  interior,  we  likewise  found  them.  There  was  nothing 
abnormal  in  the  texture  of  this  organ.  It  was  neither  harder  nor 
softer  than  ordinary ;  upon  incision  only  a  moderate  amount  of 
blood  flowed  from  it.  The  gall-bladder  contained  no  more  bile 
than  usual ;  this  bile  was  of  a  clear  yellow  color.  Nothing  unusual 
was  remarked  in  the  hepatic  canals,  cystic  and  choledochic. 

The  stomach,  small  and  contracted,  was  entirely  concealed  by 
the  liver.  Its  walls  were  hard  to  the  touch.  Its  internal  surface 
was  of  a  slate-gray  throughout  its  whole  extent,  and  mammillated. 
This  appearance  depended  upon  the  considerable  hypertrophy 
which  the  mucous  membrane  had  undergone.  This  hypertrophy 
was  unequal  in  different  parts  of  the  stomach  ;  where  it  was  very 
pronounced,  its  presence  was  announced  by  a  species  of  pimples, 
or  nipples,  and  between  them  there  were  some  depressions  in 
which  the  mucous  membrane  was  somewhat  thinned.  The  sub- 
mucous cellular  tissue  participated  a  little,  towards  the  pylorus 
especially,  in  the  thickening  of  the  membrane  which  covered  it. 

The  duodenum  presented  on  its  internal  surface  the  same 
slate-gray  tint  as  that  which  we  found  in  the  stomach.  The  re- 
mainder of  the  alimentary  canal  offered  nothing  remarkable.  The 
spleen  was  not  large,  of  average  consistence,  such,  in  a  word,  as  it 
presents  itself  when  we  regard  it  as  being  in  its  normal  condition. 
The  supra-renal  capsules  appeared  to  us  as  remarkable  by  their 
great  development.  The  urinary  apparatus  was  healthy.  A  very 
large  amount  of  black  coloring  matter  was  deposited  in  the  cellu- 
lar tissue,  either  interlobular  or  intervesicular,  of  the  lungs ;  there 
was  also  a  great  deal  of  it  in  the  bronchial  ganglia.  We  carefully 
examined  the  copper-colored  spots  with  which  several  parts  of 
the  skin  were  covered.  They  were  only  found  between  the  epi- 
dermis, which  was  not  at  all  colored,  and  the  cutis  vera,  which  was 
likewise  not  colored.  They  were  situated  in  the  rete  mucosum, 
that  portion  of  the  skin  which,  in  the  negro,  secretes  the  dark 
coloring  matter. 


Hepatic  CongesHon.  41 

The  remarks  of  Andral  in  regard  to  this  peculiar  case  are  a  lit- 
tle antiquated  ;  but  they  terminate  in  this  very  logical  conclusion: 
*'  It  is  probable  that  the  hypertrophy  of  the  liver  was  consecutive 
to  the  gastro-duodenal  inflammation."  In  fact  this  is  what  we 
should  have  a  right  to  believe,  even  if  the  subject  had  syphilis, 
for  I  do  not  know  with  what  known  form  of  hepatic  syphilis  we 
could  connect  the  liver  described  by  Andral. 

Perhaps  also  it  was  an  instance  of  true  cirrhosis,  and  this  case 
would  be  in  this  event  superposable  to  those  which  we  shall  find 
in  the  following  chapter ;  but  in  the  absence  of  any  histological 
examination,  I  have  preferred  to  consider  it  as  an  example  of 
chronic  congestion  of  the  liver.  From  a  work  by  George  Budd, 
in  all  points  remarkable,  and  which  marks  a  new  era  in  the  history 
of  diseases  of  the  liver/  we  quote  the  following  paragraph:  "All 
alcoholic  beverages,  all  the  substances  which  may  be  found  in  our 
food,  and  the  noxious  products  of  defective  digestion,  being  surely 
soluble,  are  immediately,  before  they  have  entered  the  circulation 
and  have  been  subjected  to  the  influence  of  oxygen,  conveyed  to 
the  liver,  the  circulation  of  which  they  more  or  less  influence  " 
(p.  65).  And  further:  "We  sometimes  encounter  them  (the  cir- 
rhoses)  with  temperate  persons,  so  that  it  is  necessary  that  there 
should  be  some  other  causes  than  spirituous  drinks.  There  may 
be  some  other  substances  among  the  immense  variety  of  matters 
introduced  into  the  stomach,  or  among  the  products  of  faulty 
digestion,  which,  absorbed  into  the  portal  vein,  cause,  like  alcohol, 
adhesive  inflammation  (cirrhosis)  of  the  liver.  What  these  substan- 
ces are  is  now  a  matter  for  discussion.  In  a  great  proportion  of 
the  published  cases  of  cirrhosis,  there  are  some  organic  lesions  of 
the  stomach,  and  in  the  goodly  number  of  cases  published  by 
Andral,  the  disease  seems  to  have  commenced  with  vomiting  and 
diarrhoea,  which  were,  some  time  after,  followed  by  ascites.  Very 
many  observations  seem  to  show  in  a  certain  manner  that  the 
disease  is  occasionally  produced  by  certain  substances  proceeding 
from  defective  digestion  or  from  some  errors  of  diet  other  than 
the  excessive  consumption  of  spirituous  liquors. 

"  This  conclusion  is  strongly  supported  by  the  experience  of  the 
physicians  of  the  East  Indies.  Adhesive  inflammation  of  the 
liver  leading  to  an  increase  of  its  volume,  to  its  induration,  and 
consecutively  to  positive  disturbance  of  its  functions,  is  a  common 
form  of  hepatitis  of  these  countries,  and  seems  to  result  in  part 
'  George  Budd,  On  Diseases  of  the  Liver ^  third  edition,  London,  1857. 


42  The  Liver  of  Dyspeptics. 

from  the  use  of  alcoholic  drinks,  which  are  especially  injurious  on 
account  of  the  heat  of  the  climate,  in  part  from  the  great  quantity 
of  pepper  and  strong  spices  of  different  kinds,  which  the  English 
consume  in  the  East  Indies"  (p.  150  and  following). 

Thus  it  is  as  if  fully  convinced  of  the  fact  and  not  in  the  way 
of  a  hypothesis  thatBudd  speaksof  the  role  of  the  products  of  defec- 
tive digestion  in  the  genesis,  not  only  of  hepatic  congestions,but  also 
of  cirrhosesof  theliver.  Itisforhim  an  evident  thing  which  his  clin- 
ical experience  has  demonstrated  to  him.  For  nearly  forty  years 
these  pages  have  lain  dormant  without  any  one  dreaming  of  going 
there  to  seek  once  more  for  the  pathogeny  of  the  cirrhoses,  so 
long  a  time  macerated  in  alcohol.  Frerichs  '  barely  suspects  that 
the  cirrhoses  may  have  a  more  extensive  etiology. 

"Thus  far,"  says  he,  "we  have  not  been  able  to  positively 
discover  if,  independent  of  alcohol,  there  are  other  ingesta  which, 
carried  by  the  blood  of  the  portal  vein  through  the  liver,  may 
excite  in  this  organ  an  irritation  capable  of  there  developing  a 
slow  inflammation  followed  by  induration."  Leven*  is  the  first 
contemporaneous  writer  who  systematically  treats  this  question. 
"When  the  dyspepsia,"  says  he,  "  has  lasted  for  a  certain  time,  it 
frequently  terminates  by  reacting  upon  the  liver,  producing  con- 
gestion of  this  organ  and  causing  hepatic  colics." 

He  also  cites  some  interesting  cases :  those  only  will  be  found 
here  in  which  there  is  no  question  of  biliary  lithiasis. 

Case  ii  (Leven,  case  lxxiv). 
S ,  forty  years  old,  stock-broker,  sick  for  several  years ; 


complains  especially  of  violent  headache,  of  vertigo.  He  cannot 
traverse  any  place  without  being  supported  upon  the  arm  of  a 
companion.  The  whole  left  and  median  regions  of  the  stom- 
ach are  painful  to  pressure.  He  continually  is  passing  off  gas  by 
the  mouth  and  anus.  His  stomach  is  filled  with  water  and  he 
never  vomits  ;  he  only  has  nausea.  His  fingers  and  arms  are  stiff. 
There  is  a  species  of  contracture  of  the  fingers.  The  hepatic 
region  is  painful  throughout  its  whole  extent:  the  liver  is  large , 
congested,  as  is  frequent  in  cases  of  dyspepsia  of  long  standing. 
This  patient  is  pallid,  melancholy,  and  believes  himself  obliged  to 

^  Frerichs,  Traits  pratique  des  maladies  du  foie.     Traduction  de  Dumenil  et  Pella- 
got,  3  edit.,  1877,  page  302. 

''Leven,  Traits  des  maladies  de  Vestomac,  1879. 


Hepatic  Congestion.  45 

abandon  his  business.  After  two  months'  treatment  he  was 
entirely  cured. 

I  will  incidentally  remark  that  the  tetany  was  of  gastric  origin. 
Leven  also  mentions  some  other  cases  of  it,  one  of  which  was  fol- 
lowed by  death  in  forty-eight  hours. 

Case  hi  (Leven,  case  lxxviii). 

Madame  L ,  a  widow,  forty-four  years  old,  has  had  three 

children.  Dyspeptic  for  several  years :  the  stomach  bloats  after 
meals.  Eructations  of  gas  and  flatulence;  stools  every  two  or 
three  days.  If  we  press  upon  the  epigastric  region,  no  pain  is 
produced  ;  the  liver  is  swollen,  extends  three  centimetres  beyond  the 
edge  of  the  false  ribs.  Throughout  the  whole  right  hypochondrium, 
pressure  is  very  painful.  This  woman  constantly  suffers  from  fron- 
tal neuralgia  and  weakness  of  the  legs. 

Case  iv  (Leven,  case  lxxix). 

A ,  for  a  year  past,  about  five  o'clock  in  the  afternoon, 

feels  some  twinges  of  pain,  some  burning  of  the  stomach.  For 
several  weeks  he  has  had  after  meals  some  regurgitation  of  liquid  ; 
in  the  evening,  about  ten  o'clock,  he  suffers  from  cramps  in  the 
stomach.  He  brings  up  water  and  gas.  No  sensitiveness  in  the 
region  of  the  stomach  but  acute  sensitiveness  in  the  right  hypochon- 
drium. The  liver  extends  four  centimetres  beyond  the  false  ribs; 
it  is  voluminous.  After  meals  the  patient  has  pains  in  the  jaws, 
and  embarrassment  of  speech,  and  also  some  pain  in  the  muscles 
of  the  limbs.  He  has  been  upon  a  milk  diet  for  the  last  year  but 
his  condition  has  not  been  improved. 

In  1883,  Poucel,  already  cited,  speaks  incidentally  of  the  altera- 
tions of  the  liver  consecutive  to  abnormal  digestion  as  follows : 
"  Let  us  introduce  into  the  portal  system  a  substance  less  injurious 
than  alcohol ;  lead  or  pus,  or  solely  the  altered  products  of  defective 
digestion.  These  products,  becoming  part  of  the  protoplasmic 
matter  of  the  hepatic  cells,  will  alter  the  chemical  composition, 
the  structure,  and  the  function  of  these  cellular  elements  before 
producing  any  disturbance  in  the  general  nutrition." 

But  it  is  Professor  Bouchard  who  has  most  methodically  in- 
vestigated the  condition  of  the  liver  in  patients  suffering  from 
dilatation  of  the  stomach.     "  Out  of  389  cases  of  dilatation  of  the 


44  1^^^^  Liver  of  Dyspeptics. 

stomach  that  have  come  under  my  personal  observation,"  says  he/ 
"  I  have  noticed  tumefaction  of  the  hver  in  23  per  cent.  This 
swelling  is  movable ;  it  increases,  diminishes,  and  disappears  ac- 
cording as  the  dyspepsia  grows  worse  or  improves.  Relapses 
are  frequent.  It  is  accompanied  by  soreness  or  a  feeling  of  weight 
in  the  right  hypochondrium  and  is  sometimes  complicated  with 
jaundice.  In  the  absence  of  the  information  which  an  autopsy 
would  furnish  us,  these  characteristics  make  me  consider  it  as 
probable  that  this  tumefaction  is  congestive.  It  is  solely  with 
patients  affected  with  dilatation  of  the  stomach  that  I  have  ob- 
served the  congestion  of  the  liver  of  chronic  diseases." 

This  hypertrophy  of  the  liver  in  chronic  diseases  such  as  diabetes 
mellitus,  obesity,  or  gout,  is  it  the  result  or  the  cause  of  the  dyscrasia, 
of  the  faulty  nutrition?  It  is  impossible  to  decide  this  point  at 
present,  but  it  is  probable  that  there  is  established  a  vicious  circle 
between  the  defective  nutrition  and  the  diseased  liver,  these  two 
factors  influencing  each  other  reciprocally. 

Moreover,  these  patients  are  very  frequently  dyspeptics  and 
there  is  nothing  inconsistent  in  the  hypothesis  that  their  stomachs 
react  upon  their  livers  in  order  to  produce  or  accentuate  this  con- 
gestion. Here  is  what  Professor  Bouchard  says  clinically  in  re- 
gard to  it : 

"  Independently  of  the  hepatic  congestion  which  is  connected 
with  dilatation  of  the  stomach,  we  observe,  in  certain  chronic  dis- 
eases, a  tumefaction  of  the  liver  more  considerable  and  more  per- 
sistent, capable  however  of  slow  variations  plus  or  minus,  indolent, 
and  never  accompanied  by  jaundice.  I  am  as  yet  unacquainted 
with  the  histological  characteristics  of  this  alteration  of  hepatic 
tissue.  Its  clinical  characteristics  and  its  pathological  associations 
lead  me  to  suppose  that  it  is  a  question  purely  and  simply  of  an 
increase  of  volume  of  the  hepatic  cells.  In  order  not  to  decide 
prematurely,  I  give  to  this  alteration  the  name  of  large  liverT 

Since  this  was  written,  M.  Bouchard's  list  of  cases  has  been  in- 
creased. He  has  been  kind  enough  to  furnish  me  his  unpublished 
figures  for  which  I  am  exceedingly  obliged.  Of  a  total  of  652 
large  livers,  observed  in  men  and  women,  240  were  coincident  with 
dilatation  of  the  stomach  ;  69  with  digestive  disturbances  such  as 
anorexia,  constipation,  vertigo,  which  makes  a  total  of  309  large 
livers  with  dyspeptic  patients,  or  a  proportion  of  48  per  cent. 

'  Bouchard,  Soc.  m^d.  des  hop.  1884,  et  Exposd des  iravaux  scieniijiques,  1SS6,  page 
93  et  94. 


Hepatic  Congestion.  45 

The  other  large  livers  to  the  number  of  343  were  encountered 
with  albuminurics  (164),  peptonurics  (72),  glycosurias  (28),  with 
obese  patients  (61),  and  with  various  other  patients  (16).  If  we 
take  the  statistics  concerning  dilatation  of  the  stomach  only,  we 
see  that  out  of  66^  observed  cases,  large  livers  were  encountered 
with  240  patients,  which  gives  almost  the  same  percentage.  Here 
also  is  the  table  of  cases  of  coincidence  of  dilatation  of  the  stomach 
and  large  liver  with  other  diseases : 

Dilatation  and  enlarged  liver 240 

Dilatation  +  enlarged  liver  +  peptonuria  .  .  44 
"  +         "  "     +  glycosuria.  .  .    13 

"  +         "  "     +  diabetes 60 

"  +         "  "     +  obesity 25 

+         "  "     +gout..' 12 

M.  P.  Le  Gendre,*  out  of  61  cases  of  dilatation  of  the  stomach 
(dyspeptic  or  latent),  has  twenty-four  times  found  hepatic  tume- 
faction, permanent  or  intermittent,  with  smooth  liver  most  fre- 
quently indolent,  extending  one  to  five  finger-breadths  beyond 
the  edge  of  the  ribs.  In  these  cases,  he  has  twice  noticed  trans- 
ient or  alimentary  glycosuria.  The  majority  of  these  subjects 
with  dilated  stomachs  were  of  gouty  ancestry  or  themselves  pre- 
sented many  characteristics  of  this  diathesis ;  several  suffered 
from  biliary  lithiasis  and  gravel.  M.  Hayem  ^  thinks  also  that  affec- 
tions of  the  stomach  play  a  very  important  role  in  diseases  of  the 
liver.  He  observes  in  the  first  place  that  duodenitis  is  frequent 
in  diseases  of  the  stomach  and  that  this  duodenitis  forms  the 
bond  of  union  between  gastritis  and  certain  hepatic  irritations, 
especially  those  of  the  biliary  passages.  He  next  recognizes  as  a 
pathogenic  cause  acting  upon  the  liver,  the  passage  through  the 
portal  vein,  not  only  of  microbian  toxins,  but  also  of  noxious  sub- 
stances which  arise  during  the  course  of  abnormal  stomachal  di- 
gestion ;  he  especially  incriminates  acetic  acid,  which  is  almost 
constantly  present  with  hyperpeptics. 

"  In  regard  to  these  different  points,"  says  he,  "  it  is  essential 
that  some  investigations  should  be  made  with  the  design  of  sub- 
stituting precise  ideas  for  simple  probabilities."  According  to  his 
clinical  observations,  hyperpeptic  cirrhosis  is  frequently  coincident 

'  P.  Le  Gendre,  Soc.  med  des  hopitaux,  26  fev.,  1892. 
*G.  Hayem,  Clinique  in  Bulletin  medical,  1894,  No.  49. 


46  The  Liver  of  Dyspeptics. 

with  hyperpeptic  gastritis  ;  atrophic  cirrhosis,  on  the  contrary,  with 
chronic  gastritis,  manifesting  itself  by  intense  hypopepsia  or  even 
apepsia. 

In  another  lecture,*  M.  Hayem  reports  a  very  instructive  ex- 
ample of  latent  dyspepsia  with  stomachal  dilatation  and  increase 
of  the  volume  of  the  liver.  This  case  is  worthy  of  being  reported 
in  full,  for  it  demonstrates  how  frequently  diseases  of  the  stomach 
are  concealed  under  the  mask  of  a  nervous  affection. 

Case  v  (Hayem). 

In  February,  1 891,  I  was  consulted  by  a  young  man  twenty- 
eight  years  old,  a  commercial  traveller,  of  a  puny  appearance,  with 
a  tired  and  a  little  discouraged  air.  He  informed  me  that  he  had 
been  indisposed  for  more  than  ten  years ;  that  his  indisposition, 
at  first  of  little  severity,  had  very  much  increased  during  the  past 
two  years.  That  of  which  he  complained,  was  that  he  was  not 
able  to  endure  the  air  of  close  rooms,  especially  during  the  winter, 
when  apartments  are  heated.  Under  these  circumstances,  he  has 
flashes  of  heat ;  the  blood  rushes  to  his  head  and  causes  a  painful 
sensation  in  his  forehead  and  temples.  His  head,  says  he,  feels 
as  if  it  was  in  a  vise,  his  eyes  are  injected  with  blood,  his  arteries 
beat  forcibly,  his  vision  is  disturbed,  his  cheeks  become  red  and 
burning ;  sometimes  he  can  no  longer  remain  in  the  room  and  is 
obliged  to  go  outdoors  and  inhale  deep  breaths  of  fresh  air. 

His  sensitiveness  to  confined  air  is  such  that  it  is  impossible 
for  him  to  work  in  a  closed  room.  On  the  other  hand,  he  ordi- 
narily has  cold  hands  and  feet.  These  annoyances  have  spoiled 
his  life  ;  he  is  forced  to  isolate  himself  in  order  to  take  his  meals, 
to  avoid  family  or  friendly  gatherings,  to  deprive  himself  of  the 
pleasure  of  going  to  the  theatre,  and  it  is  painful  for  him  to  thus 
flee  all  social  assemblages. 

In  addition,  he  is  afraid  of  losing  his  position,  of  no  longer  be- 
ing able  to  work.  He  has  become  impressionable,  restless ;  his 
sleep  is  broken,  not  restorative,  and  he  feels  great  general  weak- 
ness. Thinking  that  the  constipation  from  which  he  has  suffered 
so  long  a  time  was  the  cause  of  his  illness,  every  morning  for  six 
months  he  has  taken  a  dose  of  sulphate  of  soda,  and  he  has  tried 
many  other  medicines  without  result.  He  complains  of  nothing 
else.     He  has  a  good  appetite  and  claims  that  his  digestion  is 

'  Georges  Hayem,  ibid..  No.  31. 


Hepatic  Congestion.  47 

good  ;  he  has  not  grown  perceptibly  thinner  since  he  has  been  ill. 
In  a  case  of  this  kind  it  was  essential  that  there  should  be  a  care- 
ful examination.  I  found  his  tongue  shghtly  coated,  his  belly 
a  little  tense,  his  liver  slightly  swollejt,  but  not  sensitive  to  the 
touch,  and  on  auscultation  of  the  heart,  in  addition  I  noticed  a 
slight  brtiit  de  galop  and  a  blowing  murmur,  a  little  rasping,  loud- 
est over  the  apex  and  prolonged  on  the  side  of  the  armpit.  The 
patient,  moreover,  experiences  some  oppression  and  palpitation  of 
the  heart  while  ascen-ding  staircases.  At  my  first  examination  his 
stomach  did  not  appear  dilated.  I  obtained  neither  clapotage 
nor  succussion.  Nevertheless,  some  days  later,  the  signs  of  dilata- 
tion were  manifest. 

There  is  here  a  point  to  which  I  desire  to  call  your  attention. 
The  first  day,  the  patient  came  to  see  me  a  short  time  after  eating ; 
at  the  second  consultation,  several  hours  had  elapsed  since  he  had 
taken  his  last  meal.  At  different  times,  with  this  patient,  I 
thought  of  t)\Q  possibility  of  letting  a  dilatation  of  the  stomach  pass 
unperceived,  even  when  this  dilatation  was  well  pronounced,  when 
our  examination  is  made  immediately  or  a  little  after  a  meal 
when  the  stomach  is  full  and  tense. 

Moreover,  I  have  with  other  patients  found  the  same  state  of 
affairs,  which  is  liable  to  lead  us  into  error.  Lastly,  I  notice  a 
feeble  sexual  development  of  the  patient  coincident  with  hypo- 
spadias and  small  testicles,  almost  infantile,  and  I  think  that  this 
condition  may  have  contributed  to  the  patient's  melancholy.  An 
examination  of  this  patient's  gastric  juice  and  urine  furnished  me 
the  complementary  information  of  this  clinical  examination. 
Examination  of  February  15,  1891  : 

Total  chlorine =  0.386 

Fixed  chlorine..  .  .  =  0.103 
Combined  chlorine  =  0.284 

Total  acidity =  0.230 

Free  HCl =  0.036 

Liquid  rather  abundant,  filtering  quite  easily,  well  emulsioned. 
Peptones  quite  plentiful ;  syntonin  ;  lactid  acid  reaction.  As  you 
see,  it  is  a  case  of  chloro-organic  hyperpepsia.  On  account  of  the 
large  amount  of  combined  chlorine,  coincident  with  a  pronounced 
dilatation  of  the  stomach,  we  might  think  that  this  condition,  ob- 
served at  the  end  of  an  hour,  would  terminate  at  a  more  advanced 


48  The  Liver  of  Dyspeptics. 

period  of  digestion  in  a  late  hyperchlorhydria.  This  is  the  state 
of  affairs  in  a  large  number  of  cases  of  chloro-organic  hyperpepsia 
observed  at  the  end  of  an  hour  after  the  test  meal.  With  our 
patient  this  was  proven  later  on,  when,  under  the  influence  of  a 
treatment  which  tended  to  improve  his  gastric  condition,  the 
chemical  type  became  that  of  hyperchlorhydria  d'emblee. 

You  will  encounter  a  great  number  of  cases  of  this  kind.  Ex- 
amination made  on  December  24,  1892.  Removal  of  the  test 
meal  at  the  end  of  an  hour. 

Total  chlorine.  .  .  .  =  0.401 
Fixed       "       . . . .  =  0.063 

Total  acidity =  0.300 

Free  HCl =  0.160 

Combined  chlorine  =  0.178 

Liquid  abundant,  mucous.  Peptones  quite  abundant ;  feeble 
acetic  acid  reaction.  The  analysis  of  the  urine  is  not  less  interest- 
ing :  it  shows  an  increase  of  urea,  of  uric  acid,  and  chlorides,  and, 
as  abnormal  elements,  a  small  quantity  of  albumin  (less  than  a 
gram)  without  casts,  and  some  urobilin.  Before  forming  a  decisive 
opinion  in  regard  to  this  case,  it  was  in  addition  necessary  to  in- 
quire into  the  antecedents  of  the  patient  and  also  ascertain  the 
conditions  in  which  his  affection  developed  itself.  The  father  of 
this  young  man  died  quite  young  of  albuminuria;  his  mother  is 
yet  living  and  healthy,  but  has  had  migraine  almost  all  her  life. 
He  has  one  brother,  dyspeptic,  one  uncle  obese  and  another  gouty. 
He  himself  has  always  been  delicate,  but  quite  well ;  he  has  never 
had  rheumatism  or  gout.  His  diet  at  all  times  has  been  rather  in- 
ferior. He  has  not  been  dissipated  in  any  way,  but  his  family  is 
Jewish  and  their  food  is  cooked  with  a  great  deal  of  grease  and 
composed  of  heavy  and  indigestible  materials. 

He  has  been  a  commercial  traveller  for  several  years  and  fre- 
quently takes  his  meals  in  hotels  and  restaurants  where  the  food 
is  often  far  from  being  the  best.  He  is  a  man  of  regular  habits, 
very  sensible,  and  has  had  neither  cares  nor  sorrows.  What  must 
be  our  diagnosis  ?  The  nervous  symptoms  are  evidently  markedly 
predominant.  They  are  the  only  ones  in  regard  to  which  the 
patient  is  anxious  and  for  which  he  has  consulted  us. 

Taking  for  a  guide  the  treatises  on  diseases  of  the  stomach, 
you  will  see  that,  according  to  the  most  recent  authors,  these 


Hepatic  Congestion.  49 

symptoms  resemble  those  which  characterize  nervous  dyspepsia. 
This,  however,  is  not  my  diagnosis.  As  soon  as  my  examination 
was  completed,  I  recognized  the  existence  of  a  gastropathy  of 
long  standing,  organic,  with  slow  and  insidious  development,  long 
ago  having  induced  slowness  of  digestion  and  consequent  dilata- 
tion of  the  stomach  and  constipation.  In  my  opinion,  it  is  this 
affection  which  has  produced  the  general  debility  and  which  has 
reacted  upon  the  nervous  system  and  the  nutrition.  I  have  sub- 
ordinated to  it,  not  only  the  nervous  phenomena,  but  also  the 
bad  condition  of  the  liver  and  kidneys.  On  account  of  these  latter 
complications,  the  case  has  appeared  to  me  to  be  somewhat  seri- 
ous. I  believe  that  I  have  discovered  the  origin  of  all  this  series 
of  symptoms  in  the  vicious  alimentary  hygiene  which  has  exer- 
cised its  influence  since  infancy  upon  an  individual  predisposed  to 
chronic  diseases  by  his  hereditary  antecedents,  aad  who  presents 
the  appearance  of  a  weakling  and  almost  of  a  degenerate.  Per- 
haps, also,  his  stomachal  affection  is  in  part  at  least  of  hereditary 
origin,  as  a  great  number  of  clinical  cases  lead  me  to  believe  in 
the  heredity  of  gastritis  and  especially  of  hyperpeptic  gastritis. 

In  many  families  all  the  members  are  attacked  by  it :  father, 
mother,  children.  My  first  care  was  to  prescribe  rather  a  severe 
diet,  composed  especially  of  milk  and  foods  that  were  readily 
digestible.  Later  on,  and  according  to  the  circumstances,  lavage 
was  practised,  and  the  patient  at  different  times  took  bicarbonate 
of  soda.  Hydrotherapy  and  abdominal  massage  were  also  em- 
ployed. 

In  the  first  place  there  was  some  improvement  of  the  cardiac 
symptoms  :  the  blowing  murmur  soon  disappeared.  It  undoubt- 
edly was  one  of  those  bruits  considered  by  M.  Potain  as  extra- 
cardiac.  Soon  after,  the  tumefaction  of  the  liver  disappeared,  but 
for  quite  a  long  time  after  the  retrocessio7t  of  this  organ,  the  tirine 
yet  contained  marked  traces  of  urobilin. 

The  albuminuria  only  disappeared  in  October,  and  later  on, 
after  a  trip,  returned,  only  permanently  ceasing  in  March,  1892. 
The  nervous  phenomena  and  the  gastro-intestinal  symptoms  were 
much  more  obstinate  to  treatment.  At  different  times  the  g-astric 
dilatation  and  constipation  disappeared  and  there  was  a  lessening 
and  even  a  suspension  of  the  vaso-motor  disturbances.  But  the 
patient  could  only  take  proper  care  of  himself  and  have  a  suita- 
ble diet  when  he  was  in  Paris.  After  each  trip  there  was  a  longer 
or  shorter  relapse,  more  or  less  accentuated.     In  April,  1892,  he 


50  The  Live7'  of  Dyspeptics. 

commenced  to  cough  and  grow  thin  and  presented  some  signs  of 
bronchitis  of  the  right  apex  with  dulness :  a  condition  quite 
alarming,  which  made  me  fear  tuberculosis.  In  September,  1893, 
notwithstanding  the  poor  condition  of  his  health,  he  was  obliged 
to  perform  military  duty.  They  sent  him  home  at  the  end  of 
five  days,  but  this  absence  was  sufficient  to  aggravate  his  situation 
for  some  time  :  the  dilatation,  which  had  disappeared,  returned  ; 
the  flashes  of  heat  in  his  face  came  back  and  were  accompanied 
by  chilliness  and  a  livid  tint  of  the  extremities. 

The  family  of  the  patient  being  anxious  in  regard  to  his  con- 
dition, I  gave  them  to  understand  the  necessity  of  his  relinquish- 
ing his  trips  and,  starting  from  this  time,  he  commenced  to 
improve.  In  November,  1893,  the  dilatation  of  the  stomach 
finally  yielded  and  has  not  since  returned  ;  but  the  vaso-motor 
disturbances  lasted  for  some  time  longer.  All  manifestations  of 
them  ceased  tovv^ards  the  end  of  November,  1893. 

Now  (January,  1894),  the  patient  no  longer  complains,  except 
of  coughing  and  expectorating  a  little  in  the  morning.  The 
auscultatory  signs,  moreover,  are  not  marked,  and  I  have  every 
reason  to  hope  that  this  young  man  will  escape  tuberculosis. 

The  present  treatises  upon  diseases  of  the  stomach  (Bouveret, 
Debove  and  Remond,  Mathieu,  in  treatise  on  medicine)  only 
point  out  the  possibility  of  the  participation  of  the  liver  in  dys- 
peptic processes.  In  a  recent  thesis,  R.  Millon,'  a  pupil  of  MM. 
Bouchard  and  Comby,  takes  the  digestive  disturbances  of  children 
affected  with  cutaneous  diseases  into  consideration  and  the  effect 
of  these  disturbances  upon  the  liver.  "  The  liver,"  says  he, 
"  with  children  frequently  attacked  by  gastro-intestinal  disturb- 
ances, is  subject  to  astonishing  variations  of  volume  ;  these  varia- 
tions are  enormous  from  one  day  to  another  ;  the  livers  of  children 
are  veritably  elastic,  to  such  an  extent  that  an  increase  of  volume 
manifesting  itself  one  time  by  a  lowering  of  the  inferior  border 
six  centimetres  below  the  edge  of  the  ribs  may  be  reduced, 
two  days  later,  to  three  centimetres,  even  less,  and  again  be 
reproduced  three  or  four  days  after.  These  transieiit  and  fre- 
quent hepatic  congestions  have  seemed  to  us  a  strong  confirma- 
tory sign  of  a  defective  condition  of  elaboration  of  alimentary 
substances  y 

Here  is  a  summary  of  the  cases  of  Millon  in  which  the  condi- 
tion of  the  liver  was  noted. 

1  R.  Millon,  loc.  cit. 


Hepatic  Congestion.  51 

Case  vi  (Millon,  case  ii). 

Louis   P ,  nineteen  months  old,   a   fine-looking  child  ; 

•suckled  until  sixteen  months  :  since  weaning,  extremely  plentiful 
diet ;  food  in  excessive  amounts  :  the  child  is  stuffed  with  soups, 
with  starchy  vegetables,  mashed  potatoes,  carrots,  etc. ;  he  also 
eats  enormously  and  gluttonously  ;  in  addition  he  is  a  great 
drinker.  He  ordinarily  digests  well  but  has  a  tendency  to  consti- 
pation and  his  passages  smell  horribly.  His  belly  is  large  and 
distended.  There  is  clapotage  at  the  umbilicus  several  hours 
after  eating  ;  the  liver  extends  three  and  a  half  centimetres  below 
the  ribs. 

Case  vii  (Millon,  iv). 

Rene  M ,  fourteen  months  old,  was  born  in  poverty- 
stricken  surroundings ;  his  mother,  tuberculous,  was  not  able  to 
nurse  him.  Has  been  fed  on  the  nursing  bottle  with  milk  of 
poor  quality  ;  besides,  they  fed  him  other  food  very  young.  At 
the  present  time,  besides  a  litre  of  milk  which  he  drinks  daily, 
they  give  him  soups,  meat ;  he  drinks  undiluted  wine.  He  is  also 
a  puny  and  slender  child  who  does  not  yet  walk  and  has  only  six 
teeth.  His  belly  is  large,  swollen ;  he  has  some  clapotage  at 
the  umbilicus.  He  is  ordinarily  constipated  and  sleeps  badly. 
His  liver  extends  a  finger  s  breadth  below  the  ribs. 

Case  viii  (Millon,  ix). 

Joseph    C ,   fourteen    months.      Child    brought    up    on 

the  breast,  was  suddenly  weaned  three  days  ago  ;  has  been  fed 
greasy  soups  and  porridges  without  having  been  accustomed  to 
them.  Forty-eight  hours  after  weaning,  appearance  of  patches  of 
impetiginous  eczema  upon  the  face.  Liver  reaches  two  finger- 
breadths  below  ribs. 

Case  ix  (Millon,  x). 

Lucienne  B ,  two  and  a  half  years.      Eleventh  child. 

Pather  a  neuropath  and  a  drunkard.  Brought  up  on  the  bottle. 
Measles,  whooping-cough,  bronchial  catarrh,  convulsions  ;  was 
early  accustomed  to  eat  every  kind  of  food  ;  has  had  diarrhoea. 
Tendency  to  rickets.  The  belly  is  enormous;  the  liver  extends 
■downwards  one  and  a  half  finger -breadths.  The  child  digests 
everything  well  which  they  give  to  it ;  she  has  no  constipation,  but 
the  fsces  smell  badly. 


52  The  Liver  of  Dyspeptics. 

Case  x  (Millon,  xix). 

Jeanne    C^ ,    twenty-nine    months.      Weaned   too   soon 

and  very  badly  fed  ;  is  nourished  almost  exclusively  on  bread  and 
cheese ;  a  great  drinker.  Legs  slightly  incurved  ;  chondro-sternal 
chaplet ;  belly  hard,  a  little  distended.  Stomach  slightly  sensi- 
tive to  epigastric  pressure.     Liver  a  finger  s  breadth  below  ribs. 

Case  xi  (Millon,  xxiv). 

Louise    S ,     twenty-three     months.      Nursed    by    her 

mother  until  sixteen  months.  Since  weaning  and  immediately 
after,  an  excessive  amount  of  nitrogenous  food  :  bouillon,  meat, 
boiled  beef,  beef-steak ;  drinks  water  reddened  with  wine  and  a 
little  pure  wine.  Profuse  perspiration  at  night ;  habitual  consti- 
pation, eructations,  a  little  gastralgia,  no  dilatation  ;  the  liver  extends 
three  centimetres  below  the  costal  border.  This  child,  since  it  was 
weaned,  has  had  several  attacks  of  general  urticaria. 

Case  xii  (Millon,  xxv). 

Marie    P ,    eight    years.     Brought   up   on   the   bottle. 

Has  always  been  thin  and  delicate.  Child  manifestly  dyspeptic, 
polydipsic  ;  its  stomach  swells  after  meals  and  is  painful  but  not 
dilated.     Liver  reaches  slightly  below  the  false  ribs. 

Case  xiii  (Millon,  xxxvi). 

Pierre  S ,  ten  years  old,  small   and   puny,  very  thin. 

Nourished  improperly.  Has  very  little  appetite  and  is  fed  almost 
exclusively  with  black  coffee  and  cafe  au  lait.  Great  drinker,  ner- 
vous, wakens  frequently  at  night.  Habitual  constipation.  Cla- 
potage  of  the  stomach  as  far  as  the  abdomen.  Liver  large, 
extending  three  centimetres  beyond  ribs.  After  some  months' 
treatment  the  liver  resumed  its  normal  dimensions. 

Case  xiv  (Millon,  xxxviii). 

Louise  F ,  three  years  old  ;  issue  of  a  lymphatic  and 

hysterical  mother  and  of  a  nervous  and  alcoholic  father.  Since 
weaning,  various  digestive  disturbances  ;  moreover,  very  badly 
nourished  ;  drinks  a  great  deal  of  water  between  meals  and  eats 
every  kind  of  food.  She  is  a  puny  and  very  nervous  child  who 
has  had  frequent  attacks  of  diarrhoea  and  whose  belly  is  very 
much  distended.     Her  liver  is  enlarged. 


Hepatic  Congestion.  53 

Case  xv  (Millon,  xliii). 

Raymond     D ,    three    and    a    half   years    old.      Child 

brought  up  in  the  country  without  any  care ;  commenced  bottle- 
feeding  when  six  months  old  ;  weaned  when  a  year  old.  Starting 
from  this  age  has  drunk  everything,  pure  wine,  coffee,  etc.  Tend- 
ency to  rickets.  No  signs  of  dyspepsia  ;  the  liver,  a  little  large^ 
extends  a  finger's  breadth  below  the  false  ribs. 

Case  xvi  (Millon,  xlv). 

Theodore  T ,  three   years,    plainly   rachitic.      Mother 

markedly  dyspeptic.  Coarse  food  from  a  very  early  period :  poly- 
dipsic.  He  is  dyspeptic,  has  frequent  diarrhoeas,  most  generally 
fetid,  some  gastro-intestinal  atony  ;  his  belly  is  constantly  swollen  ; 
his  liver  is  large  and  reaches  two  centimetres  below  the  costal 
border. 

It  would  perhaps  be  difficult  to  define  exactly  what  we  mean 
by  congestion  of  the  liver.  "  The  congestive  processes,"  says  M. 
Chauffard,  '  "  form  in  the  pathology  of  each  organ  an  illy-defined 
region,  without  precise  limits,  occupying  so  to  speak  the  frontiers 
of  the  disease.  At  what  moment  does  simple  functional  hyper- 
aemia  become  pathological  ?  In  what  cases  does  congestion,  a 
simple  anatomical  state  so  common  and  so  variable,  deserve  to  be 
individuahzed  into  a  morbid  entity  ?  For  the  liver,  more  than  for 
any  other  organ,  the  line  of  demarcation  is  uncertain.  That  which 
we  may  say  in  a  general  way,  is  that  hepatic  congestion  only  be- 
comes a  disease  by  its  intensity  or  by  the  repetition  and  the  dura- 
tion of  the  morbid  stimulations." 

It  is  very  certain  that  it  is  a  question,  in  the  individual  case, 
of  active  congestions.  There  is  no  use  inhere  dwelling  upon  the 
symptoms  of  hepatic  congestion  which  we  shall  find  stated  in  a 
masterly  manner  by  M.  Chauffard  in  his  work,  nor  upon  the 
macroscopic  appearances  and  the  histological  modifications  of  the 
organ  in  these  cases.  I  will  solely  remind  you  of  the  sense  of 
deep  discomfort  felt  by  the  patient  in  the  right  hypochondrium, 
the  painful  tension  with  the  pain  radiating  into  the  right  shoulder ; 
the  increase  in  volume  of  the  liver;  its  sensitiveness  to  palpation ; 
the  presence  sometimes  of  an  icteric  tint  of  the  conjunctivae  and 
of  the  skin ;  the  presence  in  the  urine  of  biliary  pigments  or 
'  Chauffard,  Traite  de  m/dedne,  de  Charcot,  Bouchard,  Brissaud,  t.  iii.,  p.  778. 


54  The  Liver  of  Dyspeptics. 

urobilin ;  albuminuria  ;  alimentary  glycosuria.  All  this  is  more 
or  less  temporary,  ordinarily  without  fever,  more  or  less  pro- 
nounced, and  repeating  itself  more  or  less  frequently.  I  have  not 
devoted  my  attention  especially  to  cases  of  hepatic  congestion,, 
since  the  principal  design  of  this  work  is  to  present  the  permanent 
form  of  enlarged  liver  of  gastro-intestinal  origin,  which  will  be 
considered  in  the  next  chapter  ;  I  have  not  collected  any  observa- 
tions of  this  kind,  but  it  would  however  be  easy  for  me  to  find  a 
certain  number  of  them,  and  every  physician  may  be  sure  of  run- 
ning across  similar  livers.  I  saw  some  of  them  while  I  was  an 
interne ;  I  will  only  give  a  synopsis  of  the  two  following  cases 
which  concern  persons  whom  I  saw  frequently  and  of  which  I 
have  been  able  to  follow  the  congestive  periods. 

Case  xvii  (personal). 

Dr.  X ,  my  colleague  and  friend,  thirty  years  old.     He 

is  of  gouty  ancestry  and  is  fairly  stout  (I  do  not  dare  to  say  that 
he  is  obese).  He  has  never  been  seriously  ill.  Without  being, 
properly  speaking,  dyspeptic,  he  frequently  has  trouble  with  his 
digestion,  especially  when  he  eats  more  heartily  than  usual ;  his 
epigastrium  is  distended,  respiration  is  less  easy,  his  face  becomes 
red  ;  it  is  impossible  for  him  to  work  or  even  read  for  at  least 
two  hours,  after  meals.  Several  times  both  he  and  his  colleagues 
have  noticed  a  marked  increase  of  volume  of  his  liver,  which  then 
extends  two,  three,  sometimes  even  four  finger-breadths  beyond 
the  false  ribs,  and  which  returns  more  or  less  slowly  to  its  normal 
volume,  the  next  day  or  even  two  or  three  days  after.  At  these 
times  he  experiences  a  feeling  of  tension  in  the  right  hypochon- 
drium,  but  he  has  never  had  any  icteric  coloration,  and  has  never 
noticed  any  biliary  pigments  or  urobilin  in  his  urine. 

Case  xviii  (personal). 

A  young  woman,  twenty-six  years  old,  whose  very  significant 
family  antecedents  I  shall  not  mention,  has  had  for  some  years 
past  a  great  deal  of  trouble,  which  has  exaggerated,  out  of  all 
proportion,  her  natural  nervousness,  and  made  her,  formerly  a 
very  cheerful  person,  almost  a  neurasthenic. 

For  a  year  she  has  suffered  from  quite  severe  pain  in  her 
stomach,  especially  when  some  time  has  elapsed  since  she  has 


Hepatic  Congestion,  55 

eaten  ;  the  ingestion  of  food  quiets  this  pain,  which  leads  me  to 
beHeve  that  she  has  a  hyperpeptic  form  of  gastric  disease. 

Her  stomach,  dilated  and  splashing,  reaches  to  a  finger-breadth 
above  the  umbilicus.  Her  liver  extends  two  finger-breadths  be- 
yond the  false  ribs,  and  this  condition  is  almost  permanent ;  now 
and  then  its  volume  is  even  greater.' 

'  The  same  day  as  myself  (July  19,  1894),  Degueret,  my  friend  and  colleague, 
presented  to  the  faculty  his  thesis  entitled,  Pathological  Relations  of  the  Liver  and 
Stomach.  It  was  scarcely  a  month  previously  that  we  acquainted  each  other  with  the 
subjects  of  our  theses.  Save  in  regard  to  some  details,  our  ideas  were  in  perfect  har- 
mony. But  our  two  memoirs,  far  from  being  duplicates,  were  rather  complementary 
of  each  other.  Degueret  has  especially  studied  in  their  entirety  the  relations  of  the 
alimentary  canal  with  the  hepatic  gland  ;  he  solely  mentions,  and  as  a  probability,  the 
gastro-intestinal  origin  of  the  cirrhoses.  "  In  a  great  number  of  cases,"  says  he,  "  any- 
thing which  would  remind  us  of  alcoholism  is  lacking.  .  .  .  As  to  us,  although 
our  experience  may  be  too  limited  to  enable  us  to  pronounce  with  certainty  and  to 
bring  forward  demonstrative  facts  in  sufficient  number,  we  believe  that  it  is  legitimate 
to  consider  the  cirrhogenic  action  of  gastro-intestinal  disorders  as  infinitely  probable. 
We  know  with  what  frequency  hepatic  disturbances  supervene  with  dyspeptics," 

From  the  point  of  view  of  hepatic  congestion,  Degueret  accepts  the  theory  of  M. 
Bouchard  that :  "Congestion  of  the  liver  is  the  consequence  of  a  functional  hyper- 
activity of  the  hepatic  cell  induced  by  the  arrival  in  excess  of  toxins  [it  would  be  better 
to  say  poisons,  for  there  are  no  toxins  which  come  from  the  alimentary  canal].  .  ,  . 
The  functional  hyperactivity  of  the  liver,  supervening  under  these  conditions,  is  com- 
parable to  the  compensatory  hypertrophy  of  the  heart  which  Beau  calls  providential ; 
to  the  abundant  secretion  of  mucus  by  the  glands  of  the  gastric  mucous  membrane 
when  it  has  to  contend  against  the  irritation  of  alcohol  or  a  too  acid  gastric  juice. 
.  .  .  This  glandular  activity  does  not  take  place  without  a  pronounced  vaso-dilata- 
tion  and  a  considerable  afflux  of  blood.  If  this  state  of  affairs  is  prolonged,  the 
habitual  hyperasmia  entails  its  necessary  consequences  :  cellular  degeneration,  irrita- 
tion of  the  connective  tissue,  hyperplasia,  cirrhosis.  The  functional  disturbance  has 
gradually  led  to  the  lesion.  The  hyperchlorhydria  causes  the  gastritis  and  the  atrophy 
of  the  mucous  membrane  ;  the  prolonged  irritation  of  the  liver  by  the  toxins  leads  to 
congestion,  to  degeneration  and  cirrhosis." 

Degueret  distinguishes  two  forms  or  rather  two  processes  of  this  hepatic  conges- 
tion :  the  congestion  of  those  subjects  suffering  from  dilatation  of  the  stomach  with 
abnormal  fermentations, — a.  passive  congestion  in  which  there  is  no  acceleration  of  the 
course  of  the  blood,  but  rather  engorgement  and  stasis  ;  and  the  congestion  of  hyper- 
sthenic dyspeptics, — this  is  almost  constantly  active,  with  exaggeration  of  the  functional 
power  of  the  organ. 

In  the  first,  we  most  frequently  observe  the  signs  of  hepatic  insufficiency  ;  in  the 
second,  the  absence  of  deposits  of  urates  and  of  urobilinuria,  the  frequency  of  diar- 
rhoea, a  greenish  color  of  the  stools.  His  conclusions  are  explicit  :  *'  We  believe  that 
gastro-intestinal  disorders  have  a  considerable  influence,  if  not  the  preponderant  role, 
in  the  pathogeny  of  the  cirrhoses  of  the  liver.  There  is  no  doubt  but  that  there  are 
cirrhoses  connected  with  gastro-intestinal  disorders,  as  well  with  fermentative  dys- 
pepsias as  with  hypersthenic  dyspepsias  with  hyperchlorhydria.  Besides,  every  cause 
provocative  of  repeated  and  prolonged  congestion  of  the  liver,  is  susceptible  of  ter- 
minating in  sclerosis  of  that  organ."     Degueret  would  have  had  only  to  refer  to  the 


56  The  Liver  of  Dyspeptics. 

The  urine  contains  no  urobilin,  and  but  a  small  quantity  of 
peptones.  The  urine  has  been  examined  but  once.  The  com- 
plexion, formerly  fresh  and  rosy,  is  now  a  dirty  yellow,  without, 
however,  there  being  any  icteric  or  urobilinic  impregnation  of  the 
tissues.  These  two  cases  may  be  considered  as  benign.  We  shall 
see  how  far  these  congestive  conditions  may  extend,  and  which 
frequently  remain  in  this  oscillatory,  curable  stage,  but  which 
sometimes  terminate  in  confirmed  cirrhosis. 

communication  made  by  M.  Hanot  and  myself  to  the  Congress  held  at  Rome  in  the 
month  of  AprU,  1894,  in  order  to  see  his  conjectures  surpassed  by  actual  observation. 


CHAPTER  III. 

CONFIRMED   CIRRHOSIS   OF   THE   LIVER   OCCURRING   IN   THE 
COURSE   OF   DYSPEPSIAS. 

In  vain  have  I  searched  far  and  wide  in  medical  hterature  for 
cases  comparable  to  the  following  ones.  As  the  majority  of  the 
clinicians  who  interest  themselves  in  the  study  of  diseases  of  the 
stomach  have  hitherto  neglected  to  note  the  condition  of  the 
liver,  not  even  indicating  its  volume,  so  also  those  who  collect 
cases  of  affections  of  the  liver  only  exceptionally  pay  any  atten- 
tion to  the  condition  of  the  digestive  functions,  and  very  few,  as 
we  have  seen,  Budd,  Leven,  Bouchard,  P.  Le  Gendre,  R.  Millon, 
considering  that  the  liver  and  alimentary  canal  are  parts  of  one 
and  the  same  system,  have  studied  the  relations  which  unite  the 
pathology  of  these  three  organs — stomach,  liver,  and  intestinal 
canal. 

At  the  present  time  a  fresh  current  which  is  setting  in  this 
direction  is  attracting  the  attention  of  observers  and  this  compara- 
tively recent  subject  will  soon  be  enriched  by  a  goodly  number  of 
instructive  cases.  So  far  as  cirrhosis  is  particularly  concerned, 
after  the  publication  of  this  thesis,  it  is  to  be  hoped  that  we  shall 
see  reported  cases  similar  to  the  following : 

Case  xix  (personal). 

Hereditary  gout. — Nervousness. — Chronic  dyspepsia. — Hyperpeptic 
gastritis. — Dilatation  of  the  stomach. — Enlarged  liver  without 
icterus,  without  ascites,  without  collateral  venous  circulation, 
without  enlargement  of  the  spleen. — No  alcoholism. 

Madame   J ,   aged  fifty-five   years,    is    an    innkeeper    in 

the  suburbs  of  Paris.  We  will  at  once  remark  that,  notwith- 
standing her  occupation,  she  has  never  drunk  excessively,  either 
wine  or  liquors.  During  her  whole  life,  at  each  of  her  meals  she 
has  drunk  two  or  three  glasses  of  watered  wine,  and  never  drinks 
independently  of  her  meals,  except  in  summer  when  it  is  very 

57 


58  The  Liver  of  Dyspeptics. 

warm.  Her  father,  who  died  at  the  age  of  seventy-four  years, 
was  also  an  innkeeper  and  was  a  hard  drinker.  He  was  dyspep- 
tic for  thirty  years  and  was  always  rather  particular  about  his 
food ;  for  a  long  time  he  was  in  the  habit  of  vomiting,  especially 
during  the  latter  years  of  his  life. 

Several  times  he  vomited  red  blood.  He  was  not  stout,  and 
was  very  much  emaciated  when  he  died,  but  had  no  ascites. 
Her  father  had  two  brothers  and  one  sister,  all  three  died  at  an 
advanced  age,  between  seventy-eight  and  eighty  years,  never  hav- 
ing been  sick  during  their  lives.  Her  mother  died  at  seventy- 
four  :  she  never  drank  anything  except  at  her  meals  and  never 
had  tasted  liqueurs.  As  long  as  the  patient  could  remember,  she 
alv/ays  complained  of  her  stomach. 

For  the  last  fifteen  years  of  her  life,  she  frequently  vomited 
two  or  three  hours  after  meals,  not  solid  food  but  water  ;  it  was  a 
true  gastrorrhoea.  She  also  suffered  much  from  pain  in  the  right 
hypochondrium,  and  her  physician  bled  her  for  a  disease  of  the 
liver;  several  times  blisters  were  placed  over  the  hepatic  region. 
She  was  a  robust  woman.  She  had  fifteen  children,  five  died 
young  and  six  others  have  since  died  :  a  son  at  thirty-five  years, 
of  a  disease  of  the  heart  (angina  pectoris?).  Another  son  died  at 
sixty-three  years  of  age  of  an  accident,  and  a  third  son  at  fifty, 
also  the  result  of  an  accident  in  which  he  had  some  ribs  broken. 
One  daughter  died  at  twenty-six  years,  after  much  trouble  and 
sorrow ;  she  sometimes  slept  forty-eight  hours  consecutively. 
Another  son  died  at  thirty-eight  years  of  age  of  some  disease  of 
the  stomach.  The  patient  has  no  clear  remembrance  of  the  cause 
of  the  death  of  the  sixth  child.  Four  children  are  still  living:  a 
son  sixty-five  years  old,  stout  and  healthy,  who  has  never  suffered 
from  his  stomach  ;  a  daughter  of  sixty-eight  years,  who  has  been 
in  Chili  for  thirty-five  years,  likewise  healthy.  Another  daughter 
is  a  woman  of  fifty-seven  years  of  age,  who  for  many  years  has 
had  trouble  with  her  stomach. 

Lastly,  our  patient,  who  is  the  thirteenth  child,  Madame  J , 

is  a  thin,  lanky  woman  of  medium  height,  very  quick,  intelligent, 
recounting  her  history  perfectly.  She  had  eruptions  during  in- 
fancy but  no  adenitis  ;  she  has  not  had  any  of  the  febrile  diseases. 
When  she  was  ten  years  old  she  had  pleurisy,  from  which  she  soon 
recovered  and  from  which  she  has  experienced  no  ill  effects.  She 
menstruated  at  twelve  years  of  age,  and  always  normally  until 
the  menopause.     Married  between  twenty-two  and  twenty-three 


Co7ifirmed  Cirrhosis.  59 

years  of  age,  she  has  had  six:  children  :  pregnancies  and  labors 
have  been  normal  ;  last  of  all,  during  the  war,  she  had  a  miscar- 
riage at  seven  months  as  the  result  of  a  fall. 

Until  she  was  forty-three  years  old  (twelve  years  ago),  her 
health  was  perfect.  However,  her  occupation  of  innkeeper  neces- 
sitated some  errors  of  diet,  especially  from  the  point  of  view  of 
irregularity  of  meals.  Twelve  years  ago,  her  indisposition  com- 
menced with  an  epigastric  pain,  at  first  dull,  with  some  radiations 
to  the  left  side,  but  especially  to  the  right ;  at  the  same  time  the 
patient  experienced  extreme  fatigue  in  her  legs;  she  has  some 
varicose  veins. 

This  condition  of  affairs  lasted  about  two  years  without  the 
least  vomiting.  At  the  end  of  this  period,  the  pain  localized 
itself  in  the  right  hypochondrium,  with  a  sensation  of  weight  on 
the  same  side.  At  various  intervals  this  pain  became  more 
severe,  but  without  ever  assuming  the  acute  character  of  hepatic 
colic  ;  no  vomiting.  After  each  of  these  periods  of  exacerbation, 
which  lasted  several  days,  her  eyes  were  tinged  with  yellow,  the 
urine  became  darker,  the  excretions  were  colored  ;  this  coloration 
(bile  or  simply  urobilin?)  lasted  about  a  week.  The  patient  was 
confined  to  her  bed  two  or  three  days ;  her  physician  noticed  the 
increase  in  size  of  the  liver  and  applied  a  blister  to  the  hepatic 
region. 

For  ten  years  past  her  appetite  has  been  very  capricious  ; 
sometimes  good  and  sometimes  bad.  Digestion  has  always  been 
painful  and  is  accompanied  three  or  four  hours  after  meals  by 
yawnings,  by  stretchings,  by  a  sensation  of  weight  in  the  epigas- 
trium but  no  distension,  eructations,  or  pyrosis.  During  the 
night  her  mouth  is  dry,  her  tongue  foul,  bitter  ;  this  condition  is 
almost  continuous.  The  patient  is  ordinarily  constipated ;  she 
only  has  a  passage  once  in  two  or  three  days;  she  never  has  any 
diarrhoea,  except  sometimes  during  the  summer,  when  she  eats 
fruit.  Once  after  having  been  purged  for  three  days  with  Rubi- 
nat  water,  calomel,  and  senna,  there  was  over-purgation  and  diar- 
rhoea for  eight  days. 

For  seven  years  her  condition  remained  almost  stationary 
with  periods  of  aggravation.  On  the  29th  of  August,  1890,  she 
consulted  M.  Hanot,  who  observed  hypertrophy  of  the  liver  with- 
out jaundice,  without  increase  in  the  size  of  the  spleen,  without 
ascites,  and  without  increased  venous  abdominal  circulation,  and 
who  prescribed  the  following :  first,  in  the  morning,  a  glass  of  milk ; 


6o  The  Liver  of  Dyspeptics. 

second,  at  noon  and  at  seven  o'clock  in  the  evening ;  to  abstain 
from  soups,  stews,  sauces,  fats,  starchy  foods  (except  mashed  pota- 
toes with  milk),  acids,  and  raw  fruits ;  to  eat  little  bread  ;  third, 
at  each  meal  a  glass  of  Pougues  water  with  two  spoonfuls  of  white 
wine ;  fourth,  to  take  nothing  between  meals ;  fifth,  before  each 
meal  to  take  one  of  the  following  powders :  5,  Naphthol  /?, 
magnesia,  (aa)  0.30  for  a  powder;  sixth,  twice  a  week  to  take  in 
the  morning  while  fasting  a  soup-spoonful  of  Carlsbad  salts  dis- 
solved in  a  glass  of  hot  water.  This  treatment,  carefully  followed 
out,  produced  a  marked  improvement. 

The  patient  came  from  time  to  time  to  have  the  cautery 
applied  over  her  liver  "  when  it  was  swollen,"  and  she  said  she 
experienced  great  benefit  from  it,  as  she  suffered  at  these  times, 
and  her  eyes  became  yellow.  Her  digestion  continued  to  im- 
prove. On  the  6th  of  October,  1891,  M.  Hanot  again  saw  the 
patient. 

The  liver  was  still  enlarged.  M.  Hanot  then  added  to  the 
previous  treatment  20  centigrams  of  calomel,  to  be  taken  twice  a 
week  in  the  morning  before  eating.  January  31,  1894,  we  exam- 
ined the  patient.  We  gathered  the  preceding  information  and 
measured  the  liver.  Superiorly  this  organ  extends  to  the  level  of 
the  fourth  rib,  and  descends  into  the  abdomen  to  about  two  finger- 
breadths  from  the  crest  of  the  ilium. 

Upon  the  mammary  line,  it  measures  in  height  25  centimetres, 
on  the  axillary  line,  24  centimetres;  it  descends  15  centimetres 
below  the  xiphoid  appendix,  and  extends  towards  the  left  hypo- 
chondrium  10  centimetres  from  the  median  line.  Its  free  border, 
little  removed  from  the  crest  of  the  ilium  upon  the  axillary  line, 
remains  almost  horizontally  at  this  level  as  far  as  the  vicinity  of 
the  umbilicus,  above  which  it  extends  to  the  distance  of  two 
finger-breadths ;  it  then  takes  a  horizontal  direction  only  to 
ascend  and  disappear  under  the  left  costal  border  at  the  union  of 
its  upper  two-thirds  with  its  inferior  third.  The  border  is  uni- 
form, rounded,  but  very  perceptible,  very  hard.  The  surface  of 
the  remainder  of  the  organ  is  also  very  hard,  smooth,  and  without 
inequahties.  Palpation  is  not  painful.  The  spleen  is  not  percep- 
tible to  percussion.  The  abdojnen  is  not  distended  ;  there  is  no 
trace  of  ascites  or  any  increased  venous  circulation. 

The  stomach  is  very  much  dilated ;  clapotage  is  clearly  per- 
ceived, after  ingestion  of  half  a  glass  of  water,  at  5  centimetres 
below  the  umbilicus.     Here  are  the  results  of  the  analysis  of  her 


Confirmed  Cirrhosis.  6i 

gastric  juice  made  according  to  the  method  of  Winter  by  M. Car- 
rion, chief  of  the  chemical  laboratory  of  Professor  Hayem. 

Jan.  jy,  i8g/f..  Results  of  the  ajtalysis. 
Normal  figures  '  Hyper  +  Normal  =  Hypo- 
Total  acidity A.  .  .  .  189  264 

Free  HCl H....  44  168 

Combined  HCl C 168                                              135 

Chlorhydria H+C  ....  212  303 

Total  chlorine T  .  .  .  .  321  467 

Fixed  mineral  chlorine  .F.  . .  .  109  164 

Coefficient^^ 86  71 

Peptones pure  syntonin 

Reactions  of  HCl observed 

Residue colored 

Fatty  acids none 

Small  amount  of  liquid  (12  c.c.)  quite  well  emulsioned,  mucous. 

There  is  no  no  icterus  nor  any  urobilinic  coloration  of  the  skin  or 
conjunctiva.  The  urijte  is  of  an  amber-yellow  color,  contains  no 
sugar,  albumin,  or  urobilin.  The  urea  was  not  estimated.  Aus- 
cultation of  the  heart  and  lungs  reveals  no  alteration  of  these 
organs  ;  but  there  is  dulness  and  diminution  of  the  vesicular  mur- 
mur in  the  lower  third  of  the  right  lung ;  there  are  no  pleural 
friction  sounds. 

The  patient  is  very  nervous,  high-tempered ;  she  has  never 
had  any  nervous  crises  and  presents  no  signs  of  hysteria.  She 
belongs  to  a  gouty  family  without  herself  presenting  any  other 
signs  of  this  diathesis  except  some  white  hairs  which  commenced 
to  appear  when  she  was  forty-five  years  old,  and  some  hemor- 
rhoids which  only  date  back  to  the  menopause. 

Her  sister,  who  lives  in  Chili,  was  gray  at  thirty,  and  the  other 
sister  has  suffered  from  frequent  attacks  of  migraine,  very  severe, 
with  vomiting,  which  oblige  her  to  keep  her  bed  ;  she  frequently 
also  has  epistaxis.  The  patient  has  a  son  who  at  twenty  years  of 
age  already  had  some  white  hairs  ;  he  now  is  thirty-one,  and  his 
hair  is  quite  gray.  He  also  suffers  from  his  stomach  ;  after  meals 
he  almost  constantly  has  a  dull  pain  in  his  epigastrium  and  in  his 
back  between  the  shoulder-blades. 

The  patient,  who  has  closely  followed  the  prescribed  diet,  for 
^  All  the  numbers  express  milligrams. 


62  The  Liver  of  Dyspeptics. 

the  past  eight  days  especially,  feels  much  better  from  a  gastric 
point  of  view.  Occasionally  only,  about  three  or  four  o'clock  in 
the  afternoon,  she  has  a  little  heaviness  in  her  stomach  and  some 
yawning.  In  the  evening  she  is  tired  and  goes  to  bed  quite 
early.  She  sleeps  well  during  the  first  part  of  the  night,  but  her 
sleep  is  lighter  after  one  or  two  o'clock.  She  continually  feels 
tired  and  cannot  take  any  continuous  exercise.  We  again  saw 
the  patient  on  the  13th  of  February.  Mensuration  of  the  liver 
gives  us  24  centimetres  only  in  the  mammary  line  and  14  centi- 
metres below  the  xiphoid  appendix,  or  a  centimetre  less  than  the 
last  mensuration. 

The  dyspeptic  troubles  are  greatly  improved  ;  the  patient  eats 
and  digests  well ;  she  experiences,  after  meals,  no  pain,  no  heavi- 
ness in  the  epigastrium.  Her  tongue  is  clean.  The  urine  is 
normal ;  the  hemorrhoids  have  not  bled  for  six  weeks.  It  seems 
that,  in  order  to  terminate  in  absolute  hypertrophy,  the  liver  of 
this  woman  has  passed  through  a  variable  congestive  phase  in  the 
course  of  which  there  have  been  some  exacerbations.  Having 
once  attained  its  present  size,  the  liver  for  several  years  past  has 
remained  stationary,  manifesting  solely  at  certain  periods  some 
slight  differences,  one  or  two  centimetres  more  or  less. 

We  cannot  here  see  a  simple  chronic  congestion  ;  considering 
the  remarkable  hardness  of  the  organ,  it  is  with  a  true  cirrhosis 
that  we  have  to  deal,  and  if  none  of  the  ordinary  symptoms  of 
the  so-called  alcoholic  cirrhosis  is  present,  it  is  undoubtedly  be- 
cause the  distribution  of  the  newly  formed  connective  tissue  does 
not  sufificiently  interfere  with  the  portal  circulation  to  produce 
ascites  and  to  necessitate  a  collateral  venous  circulation. 

But  a  time  may  come,  if  a  medication,  especially  taking  into 
consideration  the  condition  of  the  alimentary  canal,  does  not 
check  the  irritative  process,  of  which  the  liver  is  the  seat,  in  which 
the  proliferation  of  connective  tissue  will  be  so  great  that  ascites 
and  an  elargement  of  the  superficial  abdominal  veins  will  manifest 
themselves.  Case  xxiv.  will  furnish  us  a  remarkable  example 
of  it.  The  same  considerations  are  applicable  to  the  two  follow- 
ing cases : 


Confirmed  Cirrhosis.  63 

Case  xx  (personal). 

Gouty  diathesis — Nervousness — Hemophilia — Dyspepsia  since  in- 
fancy— Dilatatiofi  of  the  stomach — Enlarged  liver  without 
icterus,  collateral  circulation,  ascites,  or  enlargeinent  of  the 
Spleen — No  alcoholism. 

Madame  B ,  is  forty-five  years    old.     Her  father,  who 

died  at  the  age  of  sixty,  was  obese  and  diabetic.  Her  mother, 
delicate  and  slender,  died  in  childbed  at  thirty-four.  Of  three 
children,  born  of  this  household,  one  died  young,  another,  a  boy, 
is  now  a  healthy  adult  ;  the  patient  is  the  third.  Her  health  was 
delicate  in  childhood  ;  she  had  scrofula,  some  cervical  adenitis, 
and  ciliary  blepharitis.  She  menstruated  at  eleven  years  of  age, 
and  her  menses  have  always  been  regular. 

After  marriage  she  only  had  one  pregnancy,  at  nineteen,  en- 
tirely normal.  At  thirty  years,  according  to  her  statement,  she 
had  hepatic  colic  with  vomiting,  but  without  jaundice  ;  this  pain- 
ful attack  was  of  short  duration.  At  thirty-five  years  of  age  she 
had  meningitis  (?)  which  lasted  six  weeks,  without  counting  quite 
a  long  convalescence. 

She  has  always  been  very  nervous,  without,  however,  having 
any  nervous  crises.  She  is  lively,  high-tempered,  easily  becomes 
angry,  and  is  very  impressionable.  The  news  of  the  death  of 
President  Carnot  (the  patient  came  to  see  me  on  that  day) 
affected  her  so  greatly  that  she  nearly  lost  consciousness,  and  for 
the  whole  day  was  trembling  and  weak  ;  she  had  difficulty  in 
standing  erect.  Very  frequently  she  suffers  from  pains  in  the 
head,  localized  in  the  occiput.  A  year  ago  there  was  an  increase 
in  size  of  her  thyroid  gland.  Professor  Verneuil,  who  bled  her  at 
that  time  for  menorrhagia,  which  we  will  consider  farther  on, 
several  times  injected  the  hypertrophied  gland.  At  that  time 
she  did  not  notice  that  she  had  any  trembling,  palpitations,  or 
exophthalmia,  but  she  had  some  trembling  before  this  epoch 
whenever  she  became  emotional  or  angry  ;  and  since,  she  has 
some  tachycardia  when  she  walks  a  little  too  quickly  or  ascends  a 
hill  or  a  staircase  ;  in  connection  with  this  she  also  sometimes  has 
a  slight  sensation  of  retro-sternal  anguish  with  a  tendency  to 
syncope. 

She  presents  no  sigris  of  hysteria.  Cutaneous  sensation  is 
rather  exaggerated,  but  uniformly  over  the  whole  body.  With 
her,  the  vaso-motor  phenomena  are  remarkable  :   the  least  trau- 


64  The  Liver  of  Dyspeptics. 

matism,  a  simple  rap  with  the  finger  {chiquenaude),  determines,  at 
the  contused  point,  a  lasting  redness,  and  even  a  slight  ecchymosis 
which  takes  several  days  to  absorb.  From  her  earliest  childhood 
she  has  had,  up  to  twenty-five  years  of  age,  frequent  epistaxis, 
which  was  repeated  almost  every  day  and  lasted  ten  minutes. 

Her  brother,  who,  like  her,  has  always  easily  bled  from  his 
nose,  is  yet  to-day,  at  fifty  years  of  age,  subject  to  this  accident, 
although  very  healthy.  The  menstrual  flow  of  the  patient  has 
always  been  very  abundant  and  lasts  for  eight  days.  During  her 
pregnancy,  there  was  a  slight  flow  for  the  first  four  months.  At 
the  end  of  the  sixth  month  there  was  also  some  flowing;  during 
her  confinement  she  lost  a  great  deal  of  blood.  Each  sexual 
approach  caused  a  slight  hemorrhage,  especially  with  her  hus- 
band (she  has  been  divorced  some  time  and  now  lives  with 
another  man,  less  vigorous,  she  says).  Since  the  beginning  of 
March,  1894,  she  appears  to  have  entered  into  the  period  of  the 
menopause  ;  she  has  had  some  severe  hemorrhages,  and  has  had 
to  remain  absolutely  quiet ;  her  strength  has  been  very  much 
diminished  since  this  time.  The  physician  who  then  attended 
her  said  that  she  had  a  uterine  fibroma ;  but  Professor  Verneuil, 
who  examined  her  uterus,  found  nothing  abnormal.  At  the 
present  time  (May-June,  1894)  her  menses  are  very  copious,  and 
she  has  lost  a  little  blood  every  day  during  the  whole  month  of 
June. 

I  have,  moreover,  recently  explored  the  uterus  of  this  woman, 
and  have  found  neither  increase  of  size  nor  deviation  of  this 
organ.  The  heart  beats  normally  and  auscultation  reveals  no 
murmur,  no  abnormal  sound.  The  arteries  are  neither  hard  nor 
tortuous.  The  pulse  is  very  regular ;  the  arterial  tension,  as 
well  as  it  can  be  estimated  without  apparatus,  seems  normal.  The 
patient  is  moderately  obese  ;  she  has  always  been  quite  strong. 

I  have  kept  for  the  conclusion  the  history  of  the  digestive  dis- 
turbances. I  at  once  remark  that  at  no  epoch  has  she  drunk  wine 
to  excess  ;  she  scarcely  takes  even  a  glass  of  watered  wine  with 
her  meals,  and  only  very  rarely  takes  a  small  quantity  of  liquor 
(a  finger's-breadth  in  a  small  glass).  Whenever  she  drinks  any 
undiluted  wine  or  alcoholic  drinks  it  makes  her  digestion  worse, 
already  difficult.  Between  meals  she  has  never  taken,  she  asserts, 
and  that  only  exceptionally,  anything  but  pure  water,  beer,  or 
syrups. 

At  all  times  this  woman  has  had  more  or  less  distaste  for  food. 


Confirmed  Cirrhosis.  65 

So  to  speak,  she  does  not  know  the  sensation  of  hunger ;  never 
has  it  happened  to  her  to  say  :  "Oh!  how  hungry  I  am !  "  Certain 
things  do  not  digest  well,  and  the  patient  carefully  avoids  eating 
such  dishes,  particularly  fish,  lobster,  sauces,  and  fatty  foods. 
Frequently  after  meals  she  has  acid  regurgitations  and  pyrosis. 
She  has  always  been  very  constipated,  only  going  to  stool  every 
two  or  three  days,  and  then  only  after  taking  an  enema.  For  ten 
years  she  has  had  trouble  with  her  stomach,  and  her  dyspepsia  has 
grown  worse  during  this  period. 

There  is  a  sensation  of  weight  in  the  epigastrium  after  meals  ; 
red  blotches  break  out  on  her  face,  and  there  are  patches  of  red- 
ness on  the  body,  especially  at  the  approach  of  her  menses ;  at 
these  periods,  two  or  three  hours  after  eating,  vomiting  takes 
place,  not  alimentary,  but  a  clear  and  glairy  fluid  sometimes 
tinged  with  bile.  For  ten  years  she  has  also  almost  continuously 
experienced  a  feeling  of  weight  in  the  right  hypochondrium,  which 
becomes  more  annoying  a  little  before  her  menstrual  periods. 

At  the  moment  her  menses  appear,  to  this  feeHng  of  oppres- 
sion are  added  some  painful  sensations.  Ordinarily  she  cannot 
lie  on  her  right  side  on  account  of  twinges  of  pain  in  this  side. 
After  she  has  lain  down,  if  she  suddenly  rises  and  sits  upon  her 
buttocks,  especially  if  at  this  time  her  right  thigh  is  flexed  upon 
her  pelvis,  she  has  a  bruised,  sore  feeling  in  the  right  hypochon- 
drium, followed  for  some  time  after  by  a  dull  pain. 

Occasionally  this  pain  radiates  towards  the  right  shoulder. 
Certain  movements  of  the  arms  are  always  impossible,  particularly 
their  elevation  above  the  level  of  the  shoulders  ;  the  action  of 
throwing  a  stone  produces  a  sharp  pain  in  the  hepatic  region. 
There  has  never  been  any  jaundice  ;  however,  when  she  has  her 
menses,  her  skin  assumes  a  yellowish  tint  noticeable  by  her  com- 
panions, and  her  urine  becomes  a  little  darker.  I  have  seen  this 
patient  during  and  in  the  interval  between  her  menstrual  periods  ; 
I  have  been  able  to  verify  the  absence  of  all  abnormal  coloration 
independently  of  the  time  of  the  menstrual  flux,  and,  to  the  con- 
trary, a  very  appreciable  urobilinic  impregnation  of  the  conjunc- 
tivae, scarcely  visible  in  the  skin,  during  the  catamenial  period. 

The  patient's  urine  was  examined  several  times  ;  it  was  light- 
colored,  limpid,  and  plentiful.  I  have  never  found  in  it,  even 
during  the  menstrual  period,  any  albumin,  sugar,  biliary  pigments, 
or  urobilin.  No  test  was  made  for  alimentary  glycosuria.  The 
patient  almost  constantly  has  itching,  as  she  expresses  it,  "  be- 
tween the  flesh  and  the  skin." 


66  The  Liver  of  Dyspeptics, 

No  eruption,  no  redness,  she  says,  accounts  for  it.  Tea  pro- 
vokes and  exaggerates  it  in  a  remarkable  manner.  Examina- 
tion of  the  liver,  <\\x\\.q  difficult  on  account  of  the  corpulence  of 
the  patient,  enables  us,  however,  to  exactly  determine  its  size : 
it  is  markedly  enlarged.  We  clearly  perceive  the  inferior  border 
at  1 1  centimetres  below  the  edge  of  the  false  ribs.  The  organ  is 
hard,  very  hard,  resistant,  smooth.     Palpation  is  painful. 

The  dulness  is  perceptible  in  the  mammary  line  as  high  as  the 
third  rib  and  extends  to  a  little  below  the  umbilicus.  It  meas- 
ures :  on  the  mammary  line,  27  centimetres;  on  the  xiphoid 
line,  18  centimetres;  on  the  axillary  line,  19  centimetres.  Be- 
hind, the  dulness  commences  at  the  inferior  angle  of  the  scapula. 
At  this  point  we  do  not  perceive  any  pleural  friction  sounds ; 
neither  were  they  perceived  in  the  abdomen  during  auscultation 
of  the  hepatic  region.  There  is  no  splenic  dulness,  ascites,  or  col- 
lateral venous  circulation  on  the  abdomen.  The  patient  has  some 
varicose  veins  and  sometimes,  but  rarely,  a  little  oedema  of  the 
legs.  The  stomach  is  greatly  dilated.  Percussion  and  clapotage 
enable  us  to  trace  its  great  curvature  21  centimetres  below  the 
xiphoid  appendix,  3  centimetres  below  the  umbilicus.  The 
stomachal  chemism  was  not  studied.  It  was  on  the  13th  of  April, 
1894,  that  I  first  thoroughly  examined  the  patient  and  prescribed 
for  her,  co-incident  with  an  appropriate  diet,  some  powders  con- 
taining each  30  centigrams  of  salol  and  as  much  bicarbonate  of 
soda  and  calcined  magnesia. 

On  the  30th  of  April  she  returned  much  improved  ;  she  has 
some  appetite,  she  eats  better,  she  no  longer  has  any  itching,  she 
can  He  on  her  right  side.  The  liver  is  of  the  same  size.  She  has 
only  once  had  any  pain  in  the  right  hypochondrium.  The  im- 
provement was  maintained  until  the  15th  of  June:  at  this  time 
she  had  a  severe  attack  of  menorrhagia  which  very  much  weak- 
ened her.  She  left  Paris  June  30th  in  order  to  go  into  the 
country. 

Of  the  two  preceding  cases,  for  the  present  I  shall  only  speak 
of  the  very  pronounced  nervousness  of  these  two  patients.  They 
would  almost  justify  that  phrase  of  Beau,  perhaps  more  correct 
than  at  first  sight  it  would  appear :  "  All  hysterical  persons  are 
necessarily  dyspeptic."  It  is  true  that  Beau's  conception  of  hys- 
teria was  different  from  that  of  the  present  day:  for  him, hysteria 
was  "  a  gastropathy  with  ascending  dyspnoea,  spasm  of  the  glottis, 
and  convulsions."  Pathogenically  at  least,  his  idea  of  hysteria 
was  different  from  ours. 


Co7ifirmed  Cirrhosis.  67 

Case  xxi  (personal). 

Gouty  diathesis. — No  alcokolisjn. — No  apparent  dyspepsia  before 
the  disease  of  the  liver. — Dilatation  of  the  stomach. — En- 
larged liver  without  icterus,  ascites,  collateral  circulatioji,  or 
enlargement  of  the  spleen, — Nmnerous  hemorrhages  in  the 
course  of  the  disease. 

The  said  Rosalie  N ,  aged  thirty-four  years,  charwoman, 

on  the  27th  of  January,  1894,  enters  the  service  of  Dr.  Hanot  at 
Saint  Anthony  Hospital.  The  hereditary  antecedents  are  with- 
out interest.  Her  father,  sixty-nine  years  old,  is  still  living  and 
healthy  ;  he  has  never  been  ill. 

Her  mother  died  at  fifty-nine  of  some  undetermined  affection. 
Neither  parent  was  obese,  dyspeptic,  nor  subject  to  migraine. 
Personally,  this  woman  has  always  been  comparatively  healthy : 
no  strumous  antecedents  in  infancy,  measles  at  six  years,  some 
paleness  and  anaemia  from  eleven  to  thirteen.  Her  menses,  which 
appeared  at  fifteen  years,  have  always  been  regular. 

At  eighteen  years  she  had  a  normal  pregnancy.  At  the  age 
of  twenty  years  she  came  to  live  in  Paris,  and  two  years  after 
contracted  typhoid  fever.  Starting  from  this  time  her  health  was 
excellent  until  she  was  thirty  years  old.  At  this  time,  after 
having  taken  cold  during  a  menstrual  period,  her  menses  stopped 
and  she  had  great  lassitude  and  sharp  pains  in  her  lower  extremi- 
ties. 

She  entered  La  Piti6,  where  she  remained  six  months.  Upon 
her  entrance  they  observed  that  her  liver  was  enlarged  and  that 
she  had  some  albumin  in  her  urine  ;  there  was  also  a  yellow  tint 
of  the  integuments  which  soon  disappeared,  but  no  oedema  of  the 
lower  extremities.  This  was  four  years  ago.  She  left  the 
hospital  cured,  but  for  two  years  and  a  half  her  menses  did  not 
reappear.  She  went  to  work,  feeling  quite  well,  coughing  occa- 
sionally, catching  cold  very  easily.  Her  hair  had  commenced  to 
turn  gray  during  her  sojourn  at  La  Pitie ;  at  least,  only  then  she 
perceived  it.  For  a  year  past,  without  being  obliged  to  keep  her 
bed,  without  ceasing  to  work,  her  health  is  not  so  good :  her 
strength  is  less,  her  appetite  is  diminishing.  For  six  months  her 
general  condition  has  grown  worse  ;  the  distaste  which  she  ex- 
periences for  food  is  accentuated  daily. 

In  the  first  place  she  was  not  able  to  eat  meat ;  then  she  could 
only  take  bouillon    and    milk.     However,  notwithstanding    this 


68  The  Liver  of  Dyspeptics. 

reduced  alimentation,  she  does  not  grow  thin :  on  the  contrary^ 
she  says  she  is  becoming  stouter  every  day.  For  fifteen  days 
past  she  can  no  longer  even  tolerate  milk  ;  she  vomits  it  almost  as 
soon  as  swallowed.  In  addition,  her  strength  has  diminished  and 
she  is  obliged  to  abandon  all  work. 

It  is  under  these  circumstances  that  she  enters  the  hospital. 

Condition  of  the  patient  in  Ja^iuary,  i8g^. — She  is  an  obese 
woman  whose  hair  is  almost  gray :  the  integuments  have  a  dirty 
yellow  tinge,  that  of  urobilin :  the  face  is  more  tinged  than  the 
rest  of  the  body,  and  the  conjunctivae  still  more.  She  preferably 
lies  on  her  right  side,  listless ;  she  slowly  answers  questions,  as  if 
with  difficulty,  plunged  in  a  striking  condition  of  apathy  and 
indifference. 

She  complains  of  a  cough,  but  says  nothing  of  any  localized 
pain.  The  tongue  is  a  little  foul,  moist  ;  no  appetite  ;  the  dis- 
gust for  food  is  unconquerable;  milk  even  is  rejected.  The 
stools  are  quite  regular,  the  excrements  of  normal  color.  There 
are  no  hemorrhoids.  The  liver  is  very  large  ;  its  dulness  ascends 
as  far  as  the  lower  border  of  the  fifth  rib,  and  the  lower  limit 
descends  in  the  mammary  line  to  three  finger-breadths  below  the 
umbilicus.  It  m.easures  27  centimetres  in  height.  Between  it 
and  the  median  line,  the  dulness  ascends  almost  vertically  as  far 
as  the  pit  of  the  stomach,  to  redescend  a  little  in  the  left  hypo- 
chondrium.  Palpation  is  not  easy  on  account  of  the  thickness  of 
the  panniculus  adiposus  ;  nevertheless  we  can  reach  the  lower 
border  of  the  organ,  which  is  blunt,  smooth,  without  sudden 
breaks ;  the  surface  also  appears  smooth. 

It  is  of  firm  consistence,  and  the  hand  which  has  depressed  the 
abdominal  wall  reaches  a  very  resistant  plane.  There  is  no  splenic 
dulness,  no  apparent  abdominal  venous  circulation,  save  a  lateral 
venule  scarcely  visible,  and,  moreover,  frequent  with  normal  in- 
dividuals. No  ascites.  We  do  not  perceive  any  stomachal  clapo- 
tage  ;  percussion  limits  the  boundary  of  the  stomach  to  about  a 
finger-breadth  above  the  umbilicus. 

For  seven  years,  but  especially  since  her  entrance  to  the  hos- 
pital, the  patient  has  spit  blood :  Is  it  hemoptysis,  is  it  bleeding 
from  the  gums?  It  is  difficult  to  decide;  at  one  time  the  blood 
appearing  in  frothy  strings  ;  at  another,  almost  free  from  ad- 
mixture with  the  sputa.  Auscultation  of  the  chest  does  not  solve 
the  problem  ;  sometimes  we  think  we  hear  some  subcrepitant  rales 
at  the  apices,  sometimes  sibilant,  sometimes  nothing. 


Coiifir7ned  Cirrhosis.  69 

The  heart  presents  nothing  abnormal  except  a  second  aortic 
sound  of  a  somewhat  snapping  character.  The  arteries  are  hard, 
slightly  tortuous  ;  the  pulse  beats  eighty-four  times  a  minute. 
There  are  no  varicose  veins,  no  oedema  of  the  lower  extremities. 
Since  the  beginning  of  her  present  illness,  and  perhaps  a  little 
before,  the  patient  has  had  frequent  attacks  of  epistaxis  which 
occur  almost  every  day.  The  urine  contains  urobilin  in  large 
amount ;  occasionally  there  is  albumin  ;  there  is  never  any  sugar 
or  biliary  pigments.  April  8th,  the  patient  left  the  hospital  to 
resume  her  work,  feeling  quite  well  she  said.  She  returned  on 
the  1 2th,  very  feeble,  without  appetite,  complaining  of  vertigo 
and  headache.  There  were  ecchymoses  scattered  over  her  whole 
body :  back,  chest,  thighs,  legs,  forearms,  and  arms.  There  were 
two  patches  especially,  as  large  as  the  palm  of  the  hand,  one  on 
the  anterior  and  the  other  on  the  posterior  surface  of  the  left  arm. 

In  a  few  days,  these  ecchymoses  passed  through  the  whole 
gamut  of  tints  and  disappeared  at  the  time  other  patches  were 
appearing  at  different  places.  The  epistaxis  continued  at  various 
intervals.  May  i6th,  there  were  still  some  ecchymoses,  less  nu- 
merous and  especially  less  extensive  than  the  preceding  ones. 
Epistaxis  is  less  frequent,  but  the  patient  still  coughs  and  spits 
some  blood,  without  the  auscultation  of  the  chest  revealing  any 
appreciable  lesion.  June  6th,  the  old  ecchymoses  having  dis- 
appeared, some  fresh  ones  took  their  places. 

The  patient  constantly  complains  of  weakness,  of  having 
headache  and  vertigo  and  of  suffering  from  her  stomach.  For 
some  days  past  she  has  had  a  slight  hemorrhage  from  the  vulva. 
For  three  days  she  has  felt  a  slight  pain  in  her  right  hypochon- 
drium.  Her  liver,  always  very  large,  is  sensitive  to  palpation 
and  percussion.  On  the  9th  of  June,  every  hemorrhagic  symptom 
had  disappeared,  and  the  patient,  desirous  of  going  to  work, 
again  left  the  hospital  notwithstanding  everything  we  said,  but 
she  came  back  again  about  the  15th,  this  time  with  a  severe  men- 
orrhagia.  By  June  28th,  the  menorrhagia  had  ceased.  At  this 
time  the  patient  was  in  a  condition  of  extreme  weakness  and  her 
face  was  of  a  pallor  comparable  to  that  of  those  rendered  anaemic 
by  traumatic  hemorrhages  ;  the  lips  and  conjunctivae  were  blood- 
less, the  extremities  constantly  cold  ;  the  prostration  was  very 
pronounced.  The  dimensions  of  the  liver  have  perceptibly 
diminished  ;  the  dulness  in  height  only  measures  21  centimetres. 
For  the  last  time  we  examined  the  urine,  which  invariably  con- 


70  The  Liver  of  Dyspeptics. 

tained  some  albumin,  a  little  indican,  but  no  sugar,  biliary  pig- 
ments, or  urobilin.  Auscultation  of  the  lungs,  especially  of  the 
apices,  gave  the  following  results :  resonance  preserved,  inspira- 
tion, a  little  gulping,  expiration  a  little  prolonged,  equalling  in- 
spiration, and  whistling  during  cough ;  no  rales,  no  increased 
vocal  resonance. 

The  history  of  Madame  B and  that  of  RosaUe  N 

have  a  peculiarly  interesting  side,  I  refer  to  the  severe  hemorrhages 
manifesting  themselves  under  different  forms  :  with  the  first, 
dating  from  childhood  ;  with  the  second,  only  going  back  seven 
years.  This  will  be  considered  in  the  chapter  upon  etiology. 
Case  XXL,  in  addition,  has  another  complication  :  the  continuous 
albuminuria  from  the  beginning  of  her  illness. 

It  would  not  be  within  the  scope  of  this  work  to  undertake  a 
detailed  investigation  of  the  reciprocal  relations  of  renal  and 
hepatic  affections,  inasmuch  as,  perhaps,  the  true  reason  for  the 
co-incidence  of  the  two  conditions  might  not  be  discovered.  M. 
Bouchard,  who  has  frequently  observed  either  albuminuria  or 
peptonuria  with  patients  with  enlarged  livers,  attributes  these  ^ 
conditions  to  a  defective  functioning  of  the  hepatic  cell  and  recog- 
nizes an  hepatic  albuminuria,  independent  of  every  organic  lesion 
of  the  kidneys,  the  liver  being  capable  of  causing  proteid  sub- 
stances to  undergo  a  modification  which  forces  them  to  escape 
through  the  kidneys  in  the  state  of  albumen.  He  has  also 
observed  albuminuria  with  individuals  whose  stomachs  were  di- 
lated but  whose  livers  were  not  enlarged,  in  a  less  proportion,  it 
is  true,  than  with  those  with  whom  the  liver  was  congested,  and, 
besides  hepatic  albuminuria,  he  recognizes  a  dyspeptic  albuminuria. 
Nothing  is  more  legitimate,  and  it  is  logical  to  think  that  the 
products  of  abnormal  digestion  which  are,  for  the  liver,  a  cause  of 
congestion,  and  even  of  cirrhosis,  may  also  have  upon  the  kidney 
an  injurious  action  inducing  various  lesions,  simple  congestion 
most  frequently,  sometimes  confirmed  sclerosis.  We  shall  see 
farther  on  that  a  broader  conception  may  connect  together  all 
these  phenomena  and  unite,  in  the  domain  of  the  gouty  diathesis, 
the  gastric,  hepatic,  and  renal  manifestations  of  those  people 
whose  arteries  and  connective  tissue  are  originally  fragile. 

Here  are,  although  summarized,  two  cases  of  permanent  en- 
largement of  the  liver  with  dyspeptics.  They  have  been  drawn 
up  from  the  notes  of  M.  Hanot  who,  at  several  times,  has  been 
able  to  see  the  patients. 


Confirmed  Cirrhosis.  yi 

Case  xxii  (Hanot)  unpublished. 

Dyspepsia. — No  alcoholism. — Enlarged  liver  without  icterus,  ascites^ 
collateral  abdominal  venous  circulation,  or  ejilargement  of  the 
spleen.  • 

M.  X ,  physician  practising  in  the  provinces,  came   to 

see  me  in  1887.  He  is  forty-five  years  old.  For  three  years  he 
has  suffered  from  gastro-intestinal  dyspepsia  with  incomplete 
anorexia.  Digestion  is  painful  and  followed  by  acute  and  severe 
diarrhoea.  His  liver  has  been  enlarged  for  a  year,  but  there  has 
been  no  ascites,  icterus,  or  enlargement  of  the  spleen  ;  his  liver  is 
very  hard. 

The  various  physicians  who  have  examined  him  have  diag- 
nosed his  case  as  hydatid  cyst,  cancer  of  the  liver.  In  1887,  I  note 
an  enlarged  liver  which  descends  to  within  two  finger-breadths  of 
the  umbilicus ;  this  organ  is  very  hard,  the  surface  and  inferior 
border  are  smooth.  There  is  no  splenic  dulness.  The  urine  is 
entirely  normal.  The  stomach  is  not  dilated.  At  this  particular 
time  his  dyspepsia  was  better  and  his  general  condition  good. 
From  1887  until  1892,  when  I  again  examined  the  case,  his  liver 
remained  the  same  although  the  dyspepsia  had  disappeared  and 
the  general  condition  was  still  good.     Always  absence  of  enlarged 

spleen,  of  icterus,  of  ascites,  etc.     Dr.  X has  always  been  a 

man  of  temperate  habits. 

Case  xxiii  (Hanot)  unpublished. 

Dyspepsia. — Dilatation  of  the  stomach. — Large  liver  without 
icterus,  ascites,  or  collateral  venous  circulation. — No  enlarge- 
ment of  spleen. — No  alcoholism. 

M.  X ,  railway  station-master,  aged   thirty-eight  years, 

came  to  consult  me,  in  1888,  for  some  dyspeptic  troubles  from 
which  he  had  suffered  for  eighteen  months.  Digestion  is  painful 
but  the  patient  has  never  vomited.  The  stomach  is  evidently 
dilated.  He  has  never  abused  alcohol  in  any  form.  The  liver 
reaches  three  finger-breadths  beyond  the  costal  border.  No 
ascites,  no  subcutaneous  abdominal  veins,  no  splenic  dulness,  no 
icterus. 

The  urine  contains  neither  sugar  nor  albumin.     The  patient 


72  The  Liver  of  Dyspeptics. 

drinks  little  wine  and  no  spirituous  beverages.  I  saw  him  again 
in  1889.  The  dyspepsia  has  persisted.  The  liver  now  reaches 
six  tinger-breadths  belov,'-  the  costal  border.  In  1890,  a  fresh  ex- 
ploration enabled  me  to  note  the  stationary  condition  of  the 
hepatic  hypertrophy ;  the  liver  is  still  remarkably  hard.  The 
dyspepsia,  however,  is  improved,  for  the  treatment  has  been 
aimed  in  that  direction.  In  1892,  I  found  the  liver  of  the  same 
size,  always  with  absence  of  icterus,  ascites,  or  appreciable  enlarge- 
ment of  the  spleen.  The  liver  seemed  to  me  harder  than  two 
years  previously.  The  general  condition  is  good.  The  urine  is 
normal.  The  dyspeptic  troubles  have  disappeared.  Since  this 
time,  the  health  of  the  patient,  from  whom  I  hear  occasionally,  is 
excellent.  I  know  nothing  further  in  regard  to  the  size  of  the 
liver. 

Lastly,  here  is  a  sixth  case,  the  sole  one  unfortunately  in  which 
there  was  a  histological  examination.  It  is  the  case  of  a  patient 
whom  MM.  Millard  and  Hanot  saw  several  times  and  whose  his- 
tory has  been  kindly  communicated  to  me  by  Dr.  Springer.  It 
has  been  drawn  up  from  some  detailed  notes  furnished  by  him. 

Case  xxiv  (Millard-Sprixger)  unpublished. 

Gouty  diathesis. — Gout. — Dyspepsia  of  long  standing. — Enlarged 
liver  without  icterus,  without  sple^iic  enlargeviejit,  a^id  at  first 
without  ascites  a7id  collateral  venous  circulation;  towards 
the  end.,  marked  ascites,  dilatation  of  the  abdominal  veins. — 
Death. — Autopsy  :  sclerosis  of  all  the  portal  and,  inter-trabecu- 
lar  spaces. 

Madame  C ,   aged    fifty-three    years,   presents  nothing 

particular  in  her  hereditary  antecedents.  Her  father,  a  very 
active  old  man,  is  still  living.  Her  pathological  past  only  offers 
some  temporary  accidents  ;  such  as  attacks  of  asthma  with  emphy- 
sema, which,  moreover,  completely  disappeared  two  years  ago. 
Some  slight  attacks  of  gout,  soon  quieted,  came  on  four  years 
ago,  and  no  longer  recur. 

The  psychological  past  of  this  patient,  says  Springer,  who  has 
intimately  known  her  for  a  long  time,  has  been  strangely  burdened. 
The  life  of  this  v/oman  has  been  agitated  and  unfortunate ;  not 
that  any  violent  sorrov;s  or  sudden  catastrophes  have  affected  her, 
but  an    uninterrupted  series  of  annoyances,  a  life    troublesome 


Confirmed  Cirrhosis.  J"^ 

and  trying,  had  produced  with  her  a  condition  of  permanent 
irritation  which  manifested  itself  particularly  at  her  meals ;  for  at 
that  time  were  gathered  together  those  whom  she  accused  of 
being  the  cause  of  her  misfortunes.  In  July,  1890,  the  patient 
appeared  to  be  in  excellent  health,  having  passed  the  change  of 
iife  without  accident,  when  she  was  suddenly  taken  with  sharp 
pains  in  the  right  hypochondrium.  The  manner  in  which  these 
pains  appeared,  their  lancinating  character,  and  their  seat  sug- 
gested hepatic  colic. 

Palpation  of  the  liver  revealed  nothing  abnormal  (?).  The 
patient  soon  went  with  her  family  to  the  seashore  to  pass  the 
months  of  August  and  September.  On  her  return  to  Paris  she 
had  no  suffering  and  even  had  an  excellent  appetite  ;  but  her 
physiognomy  had  completely  changed  and  her  features  were 
emaciated.  On  the  other  hand,  her  abdomen,  which  had  always 
been  large  since  her  four  pregnancies,  appeared  much  more  dis- 
tended than  formerly. 

At  this  time  we  noticed  a  little  ascites.  All  our  attention  was 
concentrated  upon  the  liver.  Its  exploration  was  easy,  owing  to 
the  emaciation  and  to  the  flexibility  of  the  abdominal  walls ;  it 
projected  seven  to  eight  centimetres  beyond  the  costal  border, 
covered  the  epigastric  region  and  even  extended  into  the  left 
hypochondrium.  Its  edge  was  sharp  and  we  could  easily  explore 
its  inferior  surface.  This  surface  was  hard,  smooth,  without  any 
inequalities,  and  its  consistence  was  uniform. 

There  was  no  increase  of  volume  of  the  spleen.  The  stomach 
was  not  dilated.  All  the  other  organs  appeared  to  be  healthy. 
Dr.  Millard,  who  then  saw  the  patient,  at  first  made  the  diagnosis 
of  hepatic  carcinoma,  but  with  some  reservations.  During  the 
whole  month  of  October,  1890,  her  belly  continued  to  swell,  the 
ascites  increased,  and  exploration  became  difficult.  On  Novem- 
ber i6th,  with  the  design  of  clearing  up  the  diagnosis,  the 
patient  was  tapped  and  two  and  a  half  litres  of  fluid  removed. 
Exploration  of  the  liver  then  revealed  no  change  in  its  dimensions 
or  characteristics.  Although  the  patient  had  never  had  syphilis, 
the  possibility  of  hepatic  syphilis  was  considered  and  a  specific 
treatment  instituted.  At  the  end  of  fifteen  days  there  was  no 
resulting  improvement. 

The  belly  constantly  increasing  in  volume  and  venous  dilata- 
tions manifesting  themselves  on  the  abdominal  wall,  we  settled 
upon  the  diagnosis  of  cirrhosis   without  qualification.     In    fact, 


74  The  Liver  of  Dyspeptics. 

there  could  be  no  question  of  alcoholism,  the  patient  never  having 
take?i  any  spirituous  liquors  and  never  having  drunk  anything  at 
her  meals  except  wine  diluted  with  ivater.  Our  inforination  is 
precise  in  regard  to  this  point.  M.  Hanot,  called  in  consultation, 
gave  the  diagnosis  of  cancer  of  the  liver.  Commencing  with  the 
month  of  January,  1891,  the  patient  rapidly  grew  weaker. 

The  digestive  functions,  however,  were  properly  performed  ; 
the  appetite  was  good,  there  was  no  distaste  for  food;  the  tongue 
was  normally  red.  Diarrhoea  was  frequent.  In  order  to  mention 
everything  which  relates  to  the  digestive  passages,  I  must  add 
that  the  patient  having  during  the  month  of  April  taken  some 
calomel  pills  (two  centigrams  daily),  which  produced  a  marked 
improvement  in  her  general  condition,  there  rapidly  supervened 
an  intense  and  very  painful  attack  of  stomatitis.  In  the  early 
part  of  June  the  patient  had  thrush,  which  quickly  yielded  to 
treatment.  Lastly,  Springer  lays  stress  upon  the  fact  that  the 
appetite  and  digestion  were  not  impaired  for  a  single  moment, 
and  that,  up  to  the  i6th  of  July,  that  is,  a  few  days  before  her 
death,  the  patient  took  a  sufficient  amount  of  nourishment.  The 
diarrhoea,  however,  was  persistent.  We  never  noticed  any  intes- 
tinal hemorrhage.  During  the  course  of  the  disease  the  patient 
was  tapped  several  times.  From  November  16,  1890,  to  July  25, 
1 89 1,  there  were  twenty-one  tappings,  by  which  one  hundred  and 
ninety  litres  of  fluid  were  removed,  or  an  average  of  nine  litres 
per  tapping.  The  hypertrophy  of  the  liver  remained  stationary 
until  May,  1891.  At  this  time  the  liver  seemed  to  diminish  in 
size,  to  retract,  while  becoming  of  a  firmer  consistence.  This  re- 
traction was  very  slow  and  little  pronounced,  for  at  the  time  of 
death,  that  is,  two  and  a  half  months  later,  the  liver  had  scarcely 
ascended  two  finger-breadths. 

At  this  time  the  dulness  extended  to  the  splenic  region,  but  it 
was  difficult  to  say  whether  it  was  due  to  hypertrophy  of  the 
spleen  or  to  development  of  the  right  lobe  of  the  liver.  The 
patient  frequently  complained  of  pains  in  this  locality.  In  the 
course  of  January,  the  subcutaneous  abdominal  veins  outlined 
themselves  more  plainly ;  the  abdominal  walls  became  the  seat  of 
a  considerable  oedema,  which  mended  a  little  under  the  influence 
of  diuretic  treatment,  but  which  soon  increased  and  invaded  the 
lower  extremities ;  nevertheless  the  patient  got  up  for  an  hour  or 
two  every  day. 

The  urine  was  plentiful  and  never  contained  either  sugar  or 


Confirmed  Cirrhosis.  75 

albumin.  Save  a  temporary  bronchitis  contracted  on  the  loth  of 
April  as  the  result  of  a  chill,  the  respiratory  apparatus  was  always 
in  good  condition.  There  was  no  lesion  of  the  heart.  M.  Hanot 
again  visited  the  patient  a  few  days  before  the  end ;  the  long 
duration  of  the  affection  appeared  to  him  to  justify  his  diagnosis 
of  cancer  of  the  liver  ;  he  refrained  from  making  any  other.  The 
patient  died  July  25,  1891.  The  family  did  not  permit  a  formal 
autopsy,  only  authorizing  an  incision  in  order  to  remove  a  portion 
of  the  liver.  This  operation  was  performed  by  Dr.  Suchard, 
histological  assistant  to  the  College  of  France,  who  made  the 
histological  examination  of  the  removed  fragment.  Here  is  the 
note  which  he  sent  to  Dr.  Springer: 

"  According  to  the  directions  which  I  had  received,  the  liver 
alone  was  to  be  examined.  Not  being  able  to  open  the  cadaver 
methodically,  I  made  through  the  abdominal  wall,  in  the  median 
line  and  below  the  xiphoid  appendix,  an  incision  three  centimetres 
in  length.  The  anterior  border  of  the  liver  appeared  between 
the  two  lips  of  the  incision,  and,  as  well  as  I  could  judge  by  the 
introduction  of  my  finger,  this  border  appeared  to  me  thickened 
and  blunt.  In  the  same  way,  I  observed  that  the  portions  of  the 
surface  of  the  liver  which  I  could  touch  were  smooth  and  pre- 
sented no  elevations,  no  depressions. 

"  The  parts  of  the  stomach  which  I  could  draw  near  the 
incision  by  the  aid  of  a  tenaculum  appeared  normal.  Acting  then 
according  to  the  instructions  which  had  been  given  me,  I  removed 
from  the  anterior  border  of  the  liver  a  piece  of  that  organ  repre- 
senting a  volume  of  about  two  cubic  centimetres.  This  fragment 
was  yellow,  bloodless  ;  the  surface  of  the  liver  forming  one  of  its 
faces  was  smooth.  Its  consistency  was  almost  elastic.  Without 
difficulty  my  finger-nail  penetrated  the  incised  surface  of  the 
section. 

"  I  noticed  the  same  physical  characteristics  on  the  portions 
of  the  liver  which  I  was  able  to  explore  by  means  of  the  finger 
introduced  into  the  abdominal  cavity.  The  incision  was  closed 
by  some  sutures.  The  fragment  removed  was  divided  so  that 
some  portions  of  it  could  be  fixed  by  osmic  acid,  others  by  alco- 
hol, and  hardened  by  the  successive  action  of  picric  acid,  gum,  and 
alcohol.  Some  sections  were  afterwards  made  of  these  portions 
of  the  liver.  Those  from  the  fragment  hardened  by  picric  acid, 
etc.,  were  stained  with  picro-carminate  of  ammonia,  and  mounted 
in  glycerine.     Examined  with  a  weak  objective,  we  there  remark 


76  The  Liver  of  Dyspeptics. 

(PI.  L,  Figs.  I  and  2) :  first,  the  integrity  of  the  central  vein  of  the 
lobule  ;  second,  the  increase  of  extent  of  the  portal  spaces.  With 
a  strong  objective,  we  easily  discover  that  the  central  veins  of  the 
lobules  are  everywhere  surrounded  by  normal  hepatic  cells ;  that 
these  central  veins  themselves  are  not  thickened ;  and,  lastly, 
that  the  capillaries  are  empty  in  the  vicinity  of  these  central 
veins. 

"  If,  with  the  same  objective,  we  examine  the  portal  spaces, 
we  see  that  the  connective  tissue,  which  surrounds  the  portal 
vein  and  the  biliary  canals,  is  very  much  more  abundant  than  in 
the  normal  condition,  and  that  at  certain  points  it  invades  the 
lobule  by  projecting  itself  around  the  compressed  biliary  canals, 
and  spreading,  so  to  speak,  between  the  intervals  of  the  hepatic 
cells. 

"  The  portal  veins  of  the  portal  spaces  contain  red  and  white 
blood  globules.  A  great  number  of  these  elements  were  scat- 
tered, by  means  of  diapedesis,  through  the  connective  tissue  of 
the  portal  spaces,  being  located  between  the  bundles  of  connect- 
ive tissue.  The  inflammatory  lesions  of  this  tissue  are  remark- 
able, and  appear  generalized  in  all  the  portal  spaces  which  I 
have  examined.  They  are  characterized  by  the  presence  of 
numerous  white  globules  and  swelling  of  the  nuclei  of  the  fixed 
tissue  cells. 

"  Moreover,  at  no  point  do  we  remark  any  collection  of  em- 
bryonic cells  sufificient  to  form  an  abscess  or  to  characterize  a 
syphilitic  gumma  of  the  liver.  In  the  preparations  obtained  by 
section,  after  fixation  of  the  tissues  by  osmic  acid,  and  examined 
in  water  with  a  strong  objective,  we  remark,  independently  of  the 
normal  condition  of  the  hepatic  cells  of  the  centre  of  the  lobule, 
the  fatty  surcharge  of  a  certain  number  of  the  peripheral  cells  of 
the  lobules,  and  granular  fatty  degeneration  of  some  cells  in  the 
vicinity  of  the  portal  spaces.  Iodine  solution  and  Paris  violet 
indicate  no  amyloid  degeneration,  either  in  the  sections  made 
before  the  addition  of  any  reagent,  or  in  the  sections  made  after 
hardening  of  the  tissues  by  the  processes  above  mentioned. 
These  lesions  being  discovered,  the  anatomical  diagnosis  is  evi- 
dently that  of  hypertrophic  cirrhosis. 

"  This  cirrhosis  is  characterized  by  chronic  lesions  (increase  of 
the  amount  of  connective  tissue  of  the  portal  spaces)  and  by  acute 
lesions  (acute  inflammation  of  this  tissue).  The  fatty  degenera- 
tion which  is  the  termination  of  the  majority  of  cases  of  cirrhosis 


Confirmed  Cirrhosis.  J  J 

is  not  yet  very  far  advanced  in  the  fragment  examined  ;  but 
nevertheless  it  is  present.  The  cause  of  this  hepatic  cirrhosis 
cannot  be  determined  by  the  examination  of  so  small  a  portion 
of  the  liver,  the  condition  of  the  other  organs  being  unknown." 

Case  xxv  (unpublished). 

Towards  the  end  of  1894,  Dr.  Levillain  (of  Nice)  sent  to  M. 

Hanot  a  patient,  the  bearer  of  the  following  note  :     "  M.  G , 

fifty-two  years  old.  Mining  superintendent.  Father  had  sci- 
atica;  sister  dead,  rachitic.  M.  G .  Infancy  :  rachitic  deformi- 
ties ;  bowed  legs.  At  seven  years  of  age  operation  for  stone  : 
then  good  general  health ;  at  fifteen,  jaundice,  consequent  upon 
emotion ;  at  twenty-five,  attack  of  appendicitis ;  at  twenty-nine, 
another  attack  of  jaundice  ;  at  forty-six,  nephritic  colic  for  three 
days ;  at  forty-eight,  itching  in  the  perinaeum,  dull  colics  in 
the  lower  belly,  vesical  tenesmus,  and  expulsion  of  gravel.  For 
a  long  time,  gastric  disorders,  stomach  always  delicate.  For 
the  last  three  or  four  years  especially,  these  troubles  are  more 
complained  of  (distaste  for  meat,  odors  of  the  kitchen  disagreeable 
and  spoiling  the  appetite);  progressive  aggravation  of  the  dys- 
peptic phenomena  (distension  of  the  stomach,  gas  and  eructations 
after  meals),  pain  in  the  gastro-hepatic  region,  which  is  sensitive 
to  pressure  and  presents  a  very  marked  dulness. 

In  addition,  and  probably  as  a  result  of  these  gastric  disturb- 
ances :  development  of  a  slight  secondary  neurasthenic  condition 
(pains  in  the  head  with  attacks  of  headache  and  painful  points), 
insomnia,  and  matutinal  amyosthenia,  clearly  coinciding  with  the 
stomach  troubles ;  psychical  asthenia,  work  more  difficult,  memory 
impaired,  urine  with  coefficient  of  insufficient  utilization  with 
traces  of  biliary  pigment. 

M.  G ,  before  consultation,  went  to  Royat,  and  took  a 

slight  course  of  thermal  treatment.  Some  gastric  disturbances 
have  come  on  which  have  led  me  to  advise  him  to  abandon  this 
treatment,  and  I  have  persuaded  him  to  seek  counsel  and  have 
his  abdominal  viscera  examined,  and  particularly  his  gastro- 
hepatic  region.  Dr.  Hanot  saw  the  patient,  and  observed  a  con- 
siderable increase  of  the  size  of  the  liver,  without  icterus,  ascites, 
increase  of  circulation,  or  enlargement  of  the  spleen.  In  consid- 
eration of  these  facts  and  a  remarkable  hardness  of  the  organ,  he 
has  not  hesitated  to  give  the  diagnosis  of  "  dyspeptic  cirrhosis." 


78  The  Liver  of  Dyspeptics. 

Here  are  found  united :  congenital  malformation  (rachitis), 
gouty  diathesis  (precocious  renal  lithiasis,  constant  digestive  dis- 
turbances), hepatic  weakness  (two  attacks  of  icterus  without  well 
determined  cause).  The  soil  was  well  prepared  for  the  develop- 
ment of  a  cirrhosis  under  the  influence  of  noxious  substances 
elaborated  in  a  diseased  alimentary  canal. 

In  order  to  condense  in  a  comprehensive  table  the  symptoms 
of  non-alcoholic  cirrhosis  of  the  liver,  caused  by  auto-intoxication  of 
gastro-intestijtal  origin,  I  will  reproduce  in  part  the  note  presented 
by  M.  Hanot  and  myself  to  the  Congress  at  Rome.  With  adults 
of  thirty-five  to  fifty-five  years  of  age  we  find,  at  the  acme  of  the 
disease,  an  enlarged  liver  projecting  four  to  eight  finger-breadths 
beyond  the  false  ribs,  measuring  20  to  25  centimetres  in  height 
on  the  mammary  line. 

Its  surface  is  uniform,  smooth,  without  indentations  or  pro- 
tuberances ;  the  edge  is  readily  perceptible,  although  a  little 
thickened.  This  organ  is  remarkably  hard ;  we  fnay  even  say 
that  it  is  almost  as  hard  as  wood.  This  is  its  most  striking  char- 
acteristic. Palpation  is  not  at  all  or  only  slightly  painful.  There 
is  no  appreciable  increase  of  the  size  of  the  spleen  ;  for  a  long 
time  no  ascites,  no  increase  of  the  collateral  abdominal  venous 
circulation  ;  never  any  icterus,  but  an  urobilinic  coloration  of  the 
integuments  which  may  also  be  lacking. 

Most  frequently  the  urine  is  normal,  it  however  may  contain 
some  urobilin  and  sometimes  more  or  less  albumin ;  we  have 
never  found  any  sugar.  If  we  interrogate  the  patients,  we  find 
no  history  of  alcoholism  (our  observations  are  precise  in  regard  to 
this  point),  neither  do  we  find  any  tuberculosis,  impaludism, 
syphilis,  or  any  apparent  cause  of  old  or  recent  infection.  But 
we  ascertain  that  for  many  years  the  patients  have  been  dys- 
peptic, either  constantly  or  intermittently,  with  or  without  dila- 
tation of  the  stomach.  With  the  patients  whom  we  have  had 
under  observation  for  some  time,  we  have  seen  the  liver  gradu- 
ally increasing  in  size,  this  organ  only  slowly  attaining  the  di- 
mensions above  mentioned.  But  at  the  beginning,  the  liver  had 
this  same  woody  hardness,  perhaps  a  little  less  pronounced  in  the 
first  place.  When  the  liver  has  attained  a  certain  degree  of  hy- 
pertrophy, this  organ  remains  almost  stationary,  and  this  for  a 
very  long  time ;  two  of  our  patients  were  under  observation  for 
seven  years.  Functional  troubles  are  complained  of  but  little. 
Independent  of  the  dyspepsia,  which  is  persistent,  save  thera- 


Confirmed  Cirrhosis.  79 

peutic  intervention,  we  notice  only  a  sensation  of  weight  in  the 
right  hypochrondrium,  some  tympanites,  habitual  constipation, 
and  a  certain  lassitude  which  renders  manual  labor  more  difficult 
and  more  quickly  fatiguing. 

However,  the  patients  are  also  subject  to  some  acute  acci- 
dents, ordinarily  temporary,  and  consisting  in  bilious  attacks 
(embarras  gastriques)  during  which  the  liver  slightly  increases  in 
size,  and  at  the  same  time  some  urobihn  appears  in  the  urine. 
The  patients  may  also  have  more  or  less  intense  attacks  of  peri- 
hepatitis which  remind  us  of  aborted  hepatic  colic.  The  termina- 
tion appears  to  take  place,  if  we  can  judge  of  it  by  the  only  fatal 
case  observed,  by  an  exaggeration  of  the  cirrhotic  process  and 
the  mechanism  habitual  to  the  so-called  alcoholic  scleroses  of  the 
liver. 

Possibly  profuse  hemorrhages,  like  those  of  Case  XX.,  might 
induce  a  fatal  termination.  We  can  then  say  that  the  prognosis 
quoad  vitam  of  such  an  affection  is  rather  favorable,  taking  into 
account,  however,  the  possibility  of  hemorrhages  and  of  a  rapid 
increase  of  the  proliferation  of  connective  tissue. 

In  addition,  such  a  liver  is  more  susceptible  than  another  to 
intercurrent  affections,  and,  as  with  all  the  cirrhoses,  the  prognosis 
is  governed  by  the  condition  of  the  hepatic  cell.  Can  there  be  an 
atrophic  cirrhosis  resulting  from  auto -intoxication  of  gastro-intest- 
inal  origin  ?  Under  the  title  of  "  A  Case  of  Hepatic  Cirrhosis 
with  Hemorrhages  from  the  Dilated  Submucous  ^Esophageal 
Veins,"  there  has  been  published  by  M.  Kutreff  ^  the  following 
case  : 

Case   XXVI   (Kutreff). 

Merchant,  aged  sixty-five  years.  Suffered  for  many  years  from 
a  periodical  flux  of  gastric  juice.  Violent  hematemesis.  Rather 
stout  and  robust.  Dilatation  of  the  heart.  Slight  arterio-scle- 
rosis.  Quite  pale.  Slight  jaundice.  Abdomen  enlarged.  Con- 
stipation. After  a  few  days  :  dryness  of  the  tongue,  insomnia, 
general  critical  Condition. 

In  consequence  of  large  rectal  enemas :  improvement.  Re- 
lapse, Distension  of  the  abdomen.  Hepatic  dulness  much  les- 
sened, that  of  the  spleen  not  increased  ;  no  sign  of  ascites.  The 
urine  contained  neither  albumin,  sugar,  nor  biliary  coloring  mat- 

'  N.  Kutreff,  Eira,  xxxviii,  15,  pp.  469-475.  Analyse  par  A.  F.  Eklund  in 
Revue  internat.  de  medecine  et de  chirurg,  pratiques,  September  25,  1894. 


8o  The  Liver  of  Dyspeptics. 

ters.  Again  improvement  as  a  result  of  same  treatment  more 
energetic.  Second  relapse,  with  hematemesis.  Chills,  slight  fever, 
with  sweating.  By  palpation  large  masses  of  solid  faeces  could 
be  detected  in  the  sigmoid  flexure.  Sweetish  and  sickening  odor 
of  the  breath. 

Agitated  and  delirious;  spasmodic  movements  of  the  arms 
and  legs.  Fatal  termination.  Autopsy :  Above  the  cardia  the 
oesophagus  was  everywhere  filled  with  true  submucous  varices, 
quite  large  and  a  little  tortuous.  The  transverse  colon  was  so 
large  that  it  occupied  the  whole  territory  between  the  ensiform 
appendix  and  the  umbilicus. 

No  ulcer  of  the  stomach,  no  cicatrix.  Common  hepatic 
cirrhosis  as  a  result  of  the  action  of  noxious  products  of  decomposi- 
tion in  the  intestinal  canal.  The  abuse  of  alcohol,  intermittent 
fever,  and  syphilis  may  be  excluded  as  etiological  factors.  The 
febrile  condition  and  the  cerebral  symptoms  were  due  to  the 
auto-intoxication  from  the  alimentary  canal. 

I  give  this  case  without  commentary  as  I  have  not  been  able 
to  see  the  original  work,  but  it  affords  matter  for  many  reflec- 
tions which  we  would  attempt  to  formulate  if  we  did  not  fear 
to  run  counter  to  sacred  dogmas  ;  some  of  them,  however,  will 
be  hazarded  a  little  later,  when  experiments  have  shown  what 
abnormal  products  are  capable  of  doing,  acids  especially,  when 
elaborated  in  a  diseased  intestinal  canal.^ 

'  Without  speaking  of  the  cases  of  infantile  cirrhosis  in  the  production  of  which  the 
action  of  alcohol  cannot  be  invoked  and  which  are  probably  caused  by  infection,  we 
must  consider  those  cases  of  cirrhosis  not  caused  by  alcohol  and  of  which  the  etiology 
is  unknown. 

If  we  wished  to  force  matters,  we  might  suspect  the  gastro-intestinal  origin  of  the 
very  interesting  cases  collected  by  Lafitte  in  his  thesis,  although  he  does  not  especially 
make  mention  of  anterior  digestive  disturbances.  It  is  much  better  to  leave  the 
pathogeny  of  these  cases  uncertain  than  to  run  the  risk  of  being  suspected  of  making 
the  facts  conform  to  the  system. 


CHAPTER  IV. 

ETIOLOGY    AND     PATHOGENY. 

That  which  perhaps  some  minds  will  admit  with  difficulty, 
is  that  the  affection  of  the  liver  of  which  we  have  just  seen  the 
two  forms,  congestion  and  cirrhosis,  is  undoubtedly  connected 
with  the  bad  condition  of  the  digestive  passages  and  finds  its 
sufficient  reason  in  an  auto-intoxication  of  gastro-intestinal  ori- 
gin. The  first  portion  of  this  work,  devoted  to  the  study  of 
the  poisons  of  the  alimentary  canal,  is,  however,  of  a  kind,  it 
would  seem,  to  induce  conviction. 

In  order  still  further  to  support  this  etiology,  I  shall  invoke 
the  aid  of  a  successful  experimentation,  the  details  of  which  will 
be  found  in  the  third  portion  of  this  work.  But  there  are  some 
objections  to  which  I  must  respond.  Consider,  they  will  say  to 
me,  the  large  number  of  dyspeptics  whom  we  encounter  and  the 
small  number  whose  livers  are  diseased. 

Consider  also  that  the  poisons  of  which  you  speak  can  be 
found  in  almost  equal  amounts  in  everybody,  and  that  the  liver 
by  means  of  increased  activity,  little  harassing,  can  transform  and 
destroy  them  ;  lastly,  you  have  only  seven  cases  of  this  so-called 
cirrhosis  and  only  one  autopsy  and  that  incomplete. 

I  will  say,  in  the  first  place,  that  in  the  past  we  have  not  suffi- 
ciently investigated  and  do  not  now  sufficiently  investigate  the 
condition  of  the  liver  in  diseases  of  the  stomach,  and  that  future 
statistics,  taking  into  consideration  this  fact,  and  not  accepting 
solely  as  capable  of  fabricating  gastro-intestinal  poisons,  those 
persons  whose  stomachs  are  manifestly  dilated,  will  show  with 
dyspeptics  a  much  larger  proportion  of  livers  at  least  congested. 

I  will  next  say  that,  if  we  are  more  or  less  well  acquainted 
with  the  list  of  poisons  which  may  originate  in  the  alimentary 
canal,  we  are  almost  completely  ignorant  in  regard  to  the  quantity 
in  which  they  are  produced,  and  especially  we  are  only  very 
imperfectly  informed  in  regard  to  their  noxious  effects  so  far  as 
the  liver  is  concerned. 

6  8l 


82  The  Liver  of  Dyspeptics. 

There  is  here  a  coefficient  which  it  is  all  but  impossible  to 
determine,  especially  if  we  take  into  consideration  the  principal 
factor,  the  individual  affected  by  the  auto-intoxication.  As  with 
infection,  the  question  of  a  suitable  terrain  here  takes  precedence 
of  every  other  pathogenic  condition.  We  must  confess  that  each 
one  of  us  has  a  manner  peculiar  to  himself  in  the  way  in  which 
he  resists  the  attacks  of  autochthonous  poisons,  and  that  the 
hepatic  cells  as  well  as  the  vessels  of  the  liver  have  in  this  respect 
a  greater  or  less  susceptibility. 

Do  we  not  see  certain  articles  of  food  well  tolerated  by  one 
stomach  which  will  produce  indigestion  in  another,  a  true  intoxi- 
cation even?  An  example  which  I  borrow  from  Chomel  shows 
the  reality  of  this  fact  of  common  observation.  "  Gamy  meats, 
so  sought  after  by  gourmets,  even  those  which  are  only 
slightly  touched,  are  poisonous  for  some  persons.  With  these 
individuals,  the  ingestion  of  such  meats  is  promptly  followed  by 
expulsion  of  faecal  matters  of  an  excessive  fetidity  recalling  that 
of  decomposed  flesh.  What  is  peculiarly  remarkable  is  that  their 
quantity  all  but  equals  that  of  the  ingested  poisonous  food. 
Other  foods  taken  at  the  same  meal  are  retained  and  well  digested  ; 
and  frequently  the  stool  of  the  next  day  is  entirely  normal." ' 

On  the  other  hand,  a  goodly  numbeTr  of  people  ingest  no 
matter  what  gamy  meats  without  being  incommoded,  even 
several  days  in  succession  or  habitually.  This  is  what  for  a  long 
time  has  been  called  idiosyncrasy.  That  which  takes  place  in  the 
stomach  or  intestine  may  equally  take  place  in  the  liver ;  and,  as 
the  gastro-intestinal  canal  shows  a  greater  or  less  susceptibility, 
so  the  liver  may  show  itself,  relatively  to  the  poisons  which  the 
afferent  vein  brings  to  it,  more  or  less  delicate,  more  or  less 
vulnerable. 

It  is  probable  that  the  hepatic  cell,  one  of  the  functions  of 
which  is  the  transformation  of  poisons,  bears  to  this  task  a  greater 
or  less  capacity,  a  greater  or  less  efficiency.  One  liver  will  not 
transform  many  a  poison ;  another  "  fears  none."  Thus  there  are 
some  stomachs  which  the  least  error  in  diet  renders  unfit  for  the 
performance  of  their  digestive  functions ;  others  "  which  can 
digest  stones." 

Then  supposing  that  all  dyspepsias  resemble  each  other, 
that  in  all  we  find  the  same  products  of  abnormal  digestion,  that 
in  every  intestine  one  and  the  same  sum  of  fermentation  and  of 

'Chomel,  Des  dyspepsias,   1857,  page  30. 


Etiology.  83 

microbian  toxins  can  be  proven,  it  will  not  remain  the  less  true 
that  this  figure  x  of  abnormal  and  poisonous  irritant  products 
will  find  a  liver  of  vascular  resistance,  of  cellular  function, 
varying  with  the  individual. 

The  question,  very  general,  moreover,  is  here  found  closely 
brought  home.  Is  there  a  reason  for  this  hepatic  idiosyncrasy  ? 
Yes,  certainly,  and  I  will  say  that  it  is  easier  to  find  than  that  of 
gastro-intestinal  idiosyncrasy.  We  might  incriminate  a  defective 
equilibrium  of  the  nervous  system,  an  innervation  more  or  less 
defective  of  the  organ,  as  we  invoke  for  the  stomach  some  re- 
flexes too  readily  put  in  action  by  many  articles  of  food.  In  fact 
there  may  be  a  nervous  dyshepatia  as  well  as  a  nervous  dyspepsia 
and  besides,  imbecillitas  ventriculi,  imbecillitas  jecoris.  I  believe 
with  my  master  Hanot,  that  the  cause  is  more  profound,  more 
organic,  if  we  may  say  so,  especially  when  it  is  a  question  of  this 
special  vulnerability  of  the  vasculo-connective  portion  of  the 
organ,  and  that  we  may  here  boldly  invoke  the  gouty  diathesis 
(arthritism). 

In  a  very  learned  and  much  noticed  lecture,  M.  Hanot ' 
endeavors  to  show  the  importance  of  predisposition  in  the  pro- 
duction of  hepatic  cirrhosis  in  general,  which  he  defines  '' as  an 
affection  for  which  the  gouty  diathesis  paves  the  way ;  which  is 
determined  by  an  intoxication  and  terminated  by  an  infection  : 
the  diathesis  rendering  easier  the  intoxication  and  the  intoxica- 
tion rendering  easier  the  final  infection." 

In  fact,  in  all  the  cases  of  cirrhosis,  nascent  or  confirmed,  in 
the  practice  of  M.  Hanot  during  the  year  1893 — a  little  more  than 
a  dozen,  while  only  counting  the  so-called  alcoholic  cirrhoses — 
we  have  found  the  gouty  diathesis  as  the  predisposing  cause. 
We  may  read  a  detailed  account  of  these  cases  in  the  excellent 
thesis  of  Dr.  A.  Le  Roux,''  who  has  brilliantly  developed  the 
ideas  of  our  master  from  this  point  of  view. 

Of  seven  cases  of  cirrhosis  which  I  present,  five  only  relate 
the  hereditary  and  personal  antecedents  of  the  patients,  and  four 
of  them  have  as  a  heading  the  words  "  gouty  diathesis."  The 
father  of  the  first  patient  (Case  xix)  was  dyspeptic  for  thirty 
years;  her  mother  always  suffered  from  her  stomach,  and  had  a 
disease  of  the  liver.     Of  fifteen  children  that  they  had,  five  died 

'  Hanot,  "  Consid.  gen.  sur  la  cirrhose  alcohol."     Sem.  me'dicale,  p.  209. 
^  A.  Le  Roux,  "  Contrib.  k  I'etude  de  la  cirrhose  hepat.  alcoholique.     Predisposi- 
tion et  precirrhose."     Thhe  de  Paris,  1894. 


84  The  Liver  of  Dyspeptics. 

young,  another  of  angina  pectoris  ;  the  patient  herself,  very  ner- 
vous, was  dyspeptic  for  many  years,  and  has  gray  hair  and  hemor- 
rhoids. Her  sister  has  very  frequently  had  epistaxis,  and  has 
suffered  from  frequent  attacks  of  migraine.  The  son  of  this 
patient  had  gray  hair  at  twenty  years  of  age,  and  has  also  suffered 
from  his  stomach. 

The  second  woman  (Case  XX)  is  the  issue  of  an  obese  and 
diabetic  father ;  she  is  very  nervous,  a  hemophile,  as  well  as  one 
of  her  brothers ;  she  is  dyspeptic  since  childhood.  The  third 
woman  (Case  xxi)  has,  so  to  speak,  no  history  ;  she  is  the  only 
hospital  patient  whom  we  have  had  under  observation.  However, 
she  is  obese,  emphysematous,  and  has  had  gray  hair  for  some 
years. 

The  fourth  (Case  XXIV)  was  gouty,  emphysematous,  and 
asthmatic.  In  the  case  of  Levillain  (Case  xxv),  the  gouty 
diathesis  was  manifested  by  precocious  renal  lithiasis  and  con- 
stant digestive  disturbances.  Lastly,  in  the  case  of  Kutreff  (Case 
XXVl),  the  patient  was  obese,  and  had  arterio-sclerosis. 

I  do  not  speak  of  the  two  cases  of  congestion  of  the  liver 
which  I  have  reported  ;  there  also  the  gouty  diathesis  is  the  key 
to  these  morbid  manifestations.  What  must  we  understand  by 
the  gouty  diathesis,  and  what  relation  has  this  constitutional  con- 
dition to  hepatic  cirrhosis  and  to  sclerotic  processes  in  general? 
I  do  not  wish  to  enter  upon  this  extensive  and  serious  question, 
which  M.  Hanot  and  his  pupil  Le  Roux  have  studied  with  all  the 
development  which  it  admits  of  ;  I  will  only  quote,  since  every- 
one is  now  agreed  in  regard  to  the  manifestations  of  this  "morbid 
temperament"  (Bouchard),  the  definition  of  my  master:  ''The 
gouty  diathesis  is  a  constitutional  condition  characterized,  among 
other  constituent  elements,  by  a  vitiation,  ordinarily  congenital 
and  hereditary,  of  the  connective  tissue  and  its  derivatives,  which 
become  tissues  of  least  resistance."  M.  Hanot  adds:  "These 
congenital  malformations  of  a  whole  system  abound  in  general 
pathology :  congenital  debility  of  the  cardio-vascular  system  of 
chlorotics,  of  the  nervous  system  with  the  hysterical  and  degen- 
erate, of  the  pulmonary  apparatus  (emphysema  and  thoracic  mal- 
formations) with  those  predisposed  to  tuberculosis,  etc." 

Placing  himself  at  a  morphological  point  of  view,  M.  Hanot, 
with  the  embryo,  very  logically  recognizes  a  defect  in  the  consti- 
tution of  the  middle  layer  of  the  blastoderm,  the  layer  from 
whence   connective   tissue   and   its   derivatives  originate.      This 


Etiology.  85 

alteration  may  be  encountered  independent  of  heredity,  in 
arthritic  children  born  of  parents  free  from  this  diathesis,  but 
physiologically  debilitated  by  infection  or  intoxication :  saturn- 
ism, alcoholism,  morphinomania,  tuberculosis,  syphilis,  etc.  ;  so 
many  causes  influencing  the  development  of  the  embryo,^  arrest- 
ing it  either  in  its  total  evolution  or  in  that  of  one  of  its  parts ; 
affecting  sometimes  the  external  layer,  of  which  the  malforma- 
tion will  be  revealed  by  tremendous  disturbances  of  the  nervous 
system,  sometimes  the  middle  layer,  and  thus  giving  rise  to 
arthritics  (Le  Roux).  "  From  a  functional  and  anatomo-patho- 
logical  point  of  view,"  again  says  M.  Hanot,  "  the  gouty  diathesis 
is  characterized  by  an  excessive  vulnerability  of  the  connective 
tissue,  with  a  tendency  to  hyperplasia,  to  fibrous  transforma- 
tion, to  fibrous  contraction."  We  find  the  same  idea  expressed 
in  almost  the  same  terms  in  a  monograph  of  Dr.  Cazalis* :  "  There 
is  with  arthritics  a  predisposition  of  the  connective  tissue,  un- 
doubtedly consequent  upon  some  defect,  to  a  special  irritability 
which,  in  the  organism,  makes  of  it  a  place  of  least  resistance, 
or  a  place  of  election  for  the  diseases  of  the  gouty  diathesis, 
whence,  with  these  patients,  the  so  frequent  inflammations  and 
prohferations  of  this  tissue  .  .  .  The  question  of  the  gouty 
diathesis  would  then  be,  above  everything  else,  a  question  of 
morphology,  and  we  will  easily  thus  comprehend  the  heredity  of 
the  diathesis." 

Fortified  with  these  data,  we  can  comprehend  why  arthritics 
alone  have  cirrhosis.  In  fact,  it  is  permissible  to  suppose  that, 
with  arthritics,  the  connective  tissue  of  the  liver,  as  well  as  the 
vascular  venous  walls,  will  be  intensely  and  profoundly  modified 
by  irritating  substances  which,  in  the  case  of  other  individuals, 
would  leave  the  organ  intact. 

"  There  is  no  disease,"  says  Cazalis,  "  without  a  predisposition 
of  the  organ  to  the  disease  which  affects  it.  All  alcoholics,  all 
syphilitics,  do  not  have  sclerosis  of  the  liver  or  spinal  cord,  and 
we  believe  that,  with  many  of  these  scleroses,  we  would  find  the 
gouty  diathesis  if  we  thought  of  looking  for  it." 

Le  Roux  very  judiciously  makes  the  remark  that  frequently 

'  See  the  report  of  the  experiments,  full  of  interest,  which  M.  Fere  communicated 
this  year  to  the  Bacteriological  Society  in  regard  to  the  production  of  malformations 
of  the  embryo  of  the  chick,  by  the  introduction  into  the  egg  of  chemical  poisonous 
substances  and  toxins, 

^  A.  Cazalis  (d'Aix-les-Bains),  Hygiine  et  regime  des  arthritiq.     Paris,  1891. 


86  The  Liver  of  Dyspeptics. 

the  individual  who  becomes  cirrhotic,  presents  the  minimum  of 
the  signs  of  the  gouty  diathesis,  the  same  also  as  he  presents  the 
minimum  of  the  signs  of  alcoholism.  It  seems  that  the  diathesis, 
as  well  as  the  intoxication,  has  had  for  the  liver  a  predilection, 
disdaining  to  attack  other  portions  of  the  organism.  To  support 
this  pathogenic  conception  of  cirrhosis  of  the  liver,  I  will  call  to 
mind  the  recent  communication  of  Professor  Verneuil  to  the 
Academy  of  Medicine.' 

This  eminent  mind  has  been  struck  by  the  connection  which 
exists  between  the  gouty  diathesis,  fragility  of  the  arteries,  and 
disease  of  the  liver.  It  is  true  that  he  otherwise  interprets  the 
relations  of  these  morbid  conditions,  and  that  he  gives  to  the 
hepatism  the  preponderant  role  in  the  production  of  hemorrhages, 
even  of  the  epistaxis  of  infancy  and  youth.  This  is  the  doctrine 
which  M.  Gl^nard  of  Lyons  has  resurrected  from  the  enthusiastic 
memoir  of  Poucel.  "  The  hepatic  lesion,"  says  this  author  (p.  14), 
"  is  the  cause  of  the  arthritic  diathesis." 

And  farther  on  (p.  104)  :  "  It  being  admitted,  according  to 
us,  that  the  congestion  of  the  liver  is  sometimes  the  cause  and 
sometimes  the  condition  of  every  disease,  it  is  important  to  state  if 
there  is  a  constant  connection  between  the  condition  of  this 
organ  and  the  diathesis  which  causes  the  morbid  predispositions. 
This  connection  is  unquestionable,  and  we  have  observed  in  a 
general  manner  that  the  maximum  increase  of  volume  of  the  liver 
corresponds  to  the  rheumatism,  to  the  gout,  to  the  lithiasis,  to 
the  diabetes,  and  that  its  reduction  takes  place  during  the  con- 
sumptive period  of  these  various  conditions.  We  add  that 
they  die  of  artJiritic  consumption  entirely  the  same  as  they  die  of 
scrofulous  consumption^  This,  it  seems  to  me,  is  taking  the  effect 
for  the  cause.  It  makes  little  difference.  I  merely  call  to  mind 
the  fact  that  two  of  my  patients  (Cases  XX  and  XXl)  have  had  a 
tendency  to  hemorrhage  :  one,  since  her  infancy  (and  that  at  the 
same  time  as  her  brother) ;  the  other,  three  years  before  the  con- 
firmed disease  of  the  liver. 

This  question  of  hemorrhages  in  cirrhoses  is  treated  by  another 
pupil  of  M.  Hanot,  Dr.  Octave  Bossu,  whose  thesis  will  appear  at 
the  same  time  as  mine,  and  in  which  will  be  again  found  my  two 
cases.  In  a  monograph  upon  "The  Etiology  of  the  Vascular  Cir- 
rhoses of  the  Liver,"  Dr.  Kabanoff,"  physician  of  the  clinic  of  Prof. 

'Verneuil,  Academie  de  medecine.     Seance  du  29  mai,  1894. 

*  N.  Kabanofi,  Archives  gendrales  de  medecine,  fevrier  et  mars,  1895. 


Etiology.  87 

Ostrooumoff  of  Moscow,  mentions  all  the  sclerotic  processes 
which  he  has  encountered  with  fourteen  cirrhotic  individuals: 
sclerosis  of  the  skin,  lungs,  myocardium,  endocardium,  blood- 
vessels, kidneys,  peritonaeum,  pleura,  and  gastro-intestinal  canal. 

He  also  mentions  epistaxis  and  hemorrhoidal  bleeding  as 
manifesting  themselves  a  long  while  before  the  cirrhosis  of  the 
liver.  For  him,  this  cirrhosis  cannot  be  considered  as  an  inde- 
pendent and  autonomous  disease,  as  a  morbid  entity,  but  as  a 
part  of  the  disease  of  the  whole  organism.  He  invokes  hereditary 
or  congenital  predisposition,  the  majority  of  his  patients  present- 
ing some  defect  or  malformation  which  made  them  true  degen- 
erates.    Some  passages  of  this  monograph  merit  quotation. 

"In  order  that  a  disease  be  produced  by  external  agents,  it  is 
necessary  that  these  act  with  great  intensity  (violent  poisons,  trau- 
matisms, etc.).  It  is  then  essential  that  something  else  aids  the 
external  action,  and  this  thing  is  \.\iQ  predisposition  of  the  organ  or 
organism  :  it  is  the  internal  etiology.  It  is  certain  that,  as  yet,  we 
know  relatively  but  little  in  regard  to  the  functioning  of  the  liver, 
much  less  than  in  regard  to  other  organs;  also  we  can  judge 
only  very  imperfectly  of  the  small  deviations  which  it  may  have 
presented  in  the  patient's  past,  variations  and  changes  which  pre- 
cisely determine  by  themselves  the  predisposition,  the  receptivity 
favoring  the  development  of  the  disease. 

"  We  must,  moreover,  consider  that  the  predisposition  is 
rarely  confined  to  one  organ,  all  the  others  remaining  absolutely 
sound.  Ordinarily  it  is  the  entire  organism  which  is  in  a  condi- 
tion of  greater  or  less  vulnerability;  the  vital  activity  is  every- 
where diminished,  metabolism  is  modified  and  disordered. 
However,  all  the  organs  do  not  participate  in  these  disturbances 
in  the  same  proportions:  one  organ  may  to  a  high  degree 
present  this  predisposition,  another  will  scarcely  feel  the  effects 
of  it. 

"  It  is  easy  to  notice,  in  fact,  that  rarely  is  a  single  organ 
diseased.  With  a  patient  affected  with  cirrhosis  it  is  extremely 
seldom  that  we  find  only  the  liver  affected  ;  several  other  organs 
ordinarily  participate  more  or  less  in  the  pathological  condition. 
In  no  case  does  cirrhosis  of  the  liver  appear  to  us  as  an  indepen- 
dent and  individualized  disease,  but  as  a  part  of  a  disease  of  the 
whole  organism,  and  constitutes,  so  to  speak,  a  complicated  symp- 
tom, a  syndrome  in  the  general  affection." 

The  conclusions  of  M.  Kabanoff  are,  first :    "  that  the  more 


88  The  Liver  of  Dyspeptics. 

strongly  the  weakness  of  organization  is  expressed  (hereditary  or 
congenital),  the  more  profound  is  the  degree  of  degeneration,  the 
sooner  commence  the  pathological  disturbances,  and  the  more 
considerable  they  are ;  and  in  such  a  terrain  very  slight  causes 
may  provoke  grave  lesions.  Secondly,  with  a  considerable  con- 
genital weakness  on  the  part  of  the  liver,  a  weakness  which,  in  the 
majority  of  cases,  if  not  in  all,  coincides  with  a  greater  or  less 
weakness  of  the  whole  organism,  the  cirrhotic  process  may  be 
provoked  by  any  external  cause,  however  insignificant." 

Thus  in  the  role  which  the  gouty  diathesis  plays  in  the  patho- 
geny of  cirrhosis,  it  is  a  question  above  everything  else  of  the 
natural  fragility  of  the  vessels  of  the  liver.  The  other  vessels  are 
not  protected  from  injury,  and  atheroma  is  the  heritage  of  the 
gouty  diathesis.  The  kidneys  do  not  escape  vascular  sclerosis 
which  sometimes  develops  without  appreciable  cause;  with  so 
much  the  more  reason  if  a  diseased  liver  permits  irritant  pro- 
ducts to  reach  them,  either  because  it  has  not  retained  or  trans- 
formed them,  or  because  it  has  elaborated  some  of  them  itself,  its 
function  being  perverted. 

We  comprehend,  therefore,  that  the  lesion  of  the  two  organs 
may  be  united,  and  that  the  pathological  condition  of  the  one 
may  react  fatally  upon  the  other.  I  have  already  spoken  of  the 
nervousness  of  two  of  my  patients  (Cases  xviii  and  xix).  This 
evidence  would  besides  show,  if  there  were  any  necessity  for 
it,  the  close  bond  which  unites  the  malformation  of  the  nervous 
cell  with  that  of  the  vasculo-connective  cell,  that  which  Charcot 
has  so  happily  expressed  by  the  term  neuro-arthritism. 


"ICT.   J. 


PL.l 


_  •/, 

'•';':, 

"via^fj 

.v.?: 

•;?, 

;•..•; 

•  •  /, 

c.:^) 

'''.'.-- 

-'■'. 

■<•.  >.'■•■.  V.  ■•; 

.  v.-..--' 

^<v^- 

.'^  •'■■■■ 

^^i^iS; 

;y::==:S^ii 


Fig. 2. 


flV/ei  dey' 


/mp.i  em  ercier,  Paris . 


Nioolet  lith. 


PLATE  I. 

Fig.  I  (Leitz,  oc.  i,  objec.  4). 

Peii-portal  and  intra-loliular  sclerosis,  with  mono-cellular  tendency.  Tlie  central 
vein  of  the  lobule  is  also  perceptil)ly  sclerosed.  Tlie  figure  does  not  show  a  slight 
degree  of  fattj'  degeneration  of  the  lobule,  entirely  marginal. 

Fig.  2  (Leitz,  oc.  i,  objec.  7). 

A  point  of  Figure  i  has  been  greatly  enlarged  in  order  to  show  the  endoperi-capil- 
lary  inflammation  and   the  penetration  of  the  connective  tissue  between  the  cellular 

spaces. 


CHAPTER  V. 

PATHOLOGICAL    ANATOMY    OF    DYSPEPTIC    CIRRHOSIS    AND    ITS 
PLACE  AMONG  THE  CIRRHOSES   OF  THE   LIVER. 

In  Case  XXIV  we  have  seen  the  result  of  the  histological  ex- 
amination made  by  M.  Suchard.  Through  his  kindness  I  have 
been  able  to  obtain  a  fragment  of  this  liver  which  I  have  cut  into 
sections  and  stained  with  the  reagents  ordinarily  employed :  picro- 
carmin,  hematoxylin,  and  eosin.  I  have  made  the  same  discoveries 
as  M.  Suchard,  but  I  will,  nevertheless,  here  dwell  upon  some 
points.     (PI.  I,  Figs,  i  and  2.) 

The  sclerosis  of  the  porto-biliary  spaces  is  generalized  ;  it  has 
no  tendency  to  form  very  large  masses  ;  it  contents  itself  some- 
times with  thickening  very  markedly  the  areolar  tissue  spaces,  and 
only  does  it  en  passant,  so  to  speak,  for  it  soon  invades  the  in- 
terior of  the  lobule.  In  fact,  the  edges  of  these  portal  plaques, 
far  from  being  sharply  defined  by  normally  arranged  hepatic 
cells,  are  sinuous,  slashed,  and  send  to  the  interior  of  the  lobules 
a  very  great  number  of  ramifications. 

If  in  some  portal  spaces  the  classic  triangular  form  is  still 
preserved,  in  the  majority  of  them  it  is  unrecognizable  on  account 
of  the  insertion  in  their  borders  of  numerous  intra-lobular  con- 
nective-tissue tracts.  In  the  sections,  we  quite  frequently  en- 
counter fibrous  lines  which  unite  two  or  even  several  portal 
spaces ;  at  some  points  the  lobules  are  thus  almost  entirely 
surrounded  by  a  ring  of  connective  tissue.  In  these  portal  spaces 
we  do  not  observe  any  new  canalicular  formation.  In  some,  the 
sclerosis  is  so  great  that  the  lumen  of  the  interlobular  vein  has 
completely  disappeared  through  endoarteritis. 

This  endoarteritis  is  continued  along  the  portal  capillaries,  in 
such  a  manner  that  some  fibrous  trabeculae,  quite  thick  some- 
times, penetrate  between  the  rows  of  hepatic  cells,  the  peri- 
capillary  inflammation  no  longer  permitting  their  junction  with 
the  cellular  spaces.      These,  although  sufficiently  respected  in 


90  The  Liver  of  Dyspeptics. 

their  arrangement,  are  disassociated  and  even  frequently  sinuous 
and  distorted. 

This  condition  does  not  reach  to  the  extent  of  their  disposition 
in  a  whorl,  which  we  see  in  certain  forms  of  syphilitic  sclerosis. 
In  the  vicinity  of  the  portal  spaces  we  encounter  some  cellular 
groups  completely  encompassed  by  fibrous  tissue.  The  central 
vein  of  the  lobule,  unaffected  in  some  lobules,  in  others  is 
markedly  thickened  ;  as  for  the  portal  space,  we  see  starting 
from  its  circumference  and  at  certain  points  only,  lines  of  con- 
nective tissue  which  insinuate  themselves  between  the  cells  in 
the  direction  of  the  radius  of  the  lobule  and  also  interrupt  the 
cellular  spaces. 

So  that,  in  certain  lobules  there  is  really,  by  virtue  of  the  con- 
sensus of  the  bi-venous  sclerosis,  a  true  monocellular  cirrhosis. 
The  fatty  degeneration  of  the  cells  is  of  but  small  moment.  It 
is  more  markedly  observed  at  the  periphery  of  certain  lobules, 
close  to  the  portal  spaces,  reminding  us  of  that  which  Sabourin 
has  described  under  the  name  of  fatty  nodular  cirrhosis ;  but  in 
many  of  the  lobules  the  cells  are  unaffected.  Upon  the  whole^  it 
is  a  question  of  a  diffused  generalized  interstitial  hepatitis  with 
monocellitlar  tendency.  From  a  macroscopic  point  of  view,  we 
only  know  that  the  liver  was  large,  smooth,  and  elastic.  We  are 
struck  with  the  analogy  which  such  alterations  present  with  those 
of  the  liver  of  certain  tuberculous  alcoholics,  which  have  been 
described  under  the  name  oi  fatty  hypertrophic  cirrhosis.  There 
is  only  lacking  here  the  more  generalized  steatosis.  Such  has 
been  the  reflection  of  M.  Sabourin,  who  has  been  kind  enough  to 
examine  my  preparations.  I  borrow  from  the  thesis  of  Bouygues 
the  histological  description  of  this  cirrhosis  investigated  in  the 
first  place  simultaneously  by  Hutinel  and  Sabourin,  then  by  Gil- 
son,  Bellange,  Hanot  and  Lauth,  etc. 

"  The  tissue  is  strewn  with  irregular  fibrous  bands  describing 
a  rounded  course  and  appearing  to  form  complete  rings.  Some- 
times a  true  annular  cirrhosis  is  formed,  but  most  frequently  the 
rings  are  incomplete  and  terminate  by  radiating  into  the  interval 
between  the  hepatic  cells.  The  sclerosis  presents  its  maximum  of 
thickness  at  the  level  of  the  portal  spaces  ;  it  is  there  that  it 
seems  to  have  commenced,  and  by  referring  to  the  forms  we  have 
studied,  we  see  that  it  is  there  that  we  find  the  first  traces  of 
inflammation. 

"  From  the  portal  space   the   sclerosis  radiates  in   different 


Pathological  Anatomy.  91 

directions,  arising  by  large  bands  of  connective  tissue  or  irregular 
tracts  which  tend  to  coalesce  and  to  join  together  the  supra- 
hepatic  veins.  It  thus  divides  the  liver  into  a  great  number  of 
irregular  rings,  comprehending  not  an  entire  lobule,  but  portions 
of  lobules,  sometimes  fragments  of  two  neighboring  lobules.  We 
notice,  besides,  a  certain  irregularity  in  this  distribution,  and  by 
the  side  of  one  small  island,  in  which  the  cells  are  but  little  dis- 
associated by  the  newly  formed  tissue,  we  see  others  in  which  the 
elements  are  completely  disaggregated.  The  edges  of  the 
sclerosed  bands  are  not  cleanly  cut,  as  in  the  systematic  annular 
cirrhosis.  We  see  sclerosed  tracts  starting  from  them  which 
penetrate  between  the  neighboring  cells  and  separate  them. 
These  tracts  are  blended  with  the  walls  of  the  intra-lobular 
capillaries  which  they  thicken,  penetrating  sometimes  very  deeply 
into  the  interior  of  the  lobule.  If  the  cirrhosis  is  of  long  stand- 
ing, the  rows  of  cells  may  be  almost  completely  disaggregated,  so 
as  to  give  to  the  liver  the  appearance  of  a  monocellular  cirrhosis. 
The  sclerotic  process  presents  in  some  cases  a  tendency  to  dif- 
fusion, which  appears  to  be  one  of  its  principal  characteristics." 

It  seems  to  me  that  a  comparison  of  these  two  anatomo-patho- 
logical  forms  shows  a  pathological  connection.  Does  not  the 
idea  naturally  present  itself  to  the  mind  that,  the  hypertrophic 
cirrhosis  of  the  tuberculous  may  also  invoke  for  its  cause  an  auto- 
intoxication of  gastro-intestinal  origin  ?  While  recognizing  the 
fact  that  tuberculosis,  let  it  be  actually  represented  in  the  liver 
by  the  bacillus  of  Koch  or  its  toxin,  may  have  a  sclerogenic 
action  (the  nodular  hepatitis  would  be  suiificient  to  prove  this) ; 
while  admitting  that  the  abuse  of  alcohol,  even  at  a  remote  period 
in  the  history  of  the  patient,  may  facilitate  this  sclerosing  action 
or  itself  take  part  in  the  process,  we  must  also  consider  the  fact 
that  the  stomach  and  intestine  are  rarely  unaffected  by  the  lesion. 

The  swallowed  expectoration  contains,  so  far  as  microbes  are 
concerned,  only  the  bacillus  of  Koch,  and,  so  far  as  regards  chemi- 
cal or  bacterian  products,  only  tuberculin.  There  is  frequently 
some  mucous  gastritis,  dilatation  of  the  stomach,  alimentary 
stasis,  and  consequent  abnormal  fermentations.  With  an  organism 
debilitated  like  that  of  a  patient  with  advanced  phthisis,  the  toxic 
irritations  have  a  more  powerful  effect,  and  perhaps  a  part  of  the 
diffused  sclerosis  is  due  to  poisons  of  gastro-intestinal  origin 
absorbed  by  the  portal  vein.  Such  a  liver  is  not  encountered 
solely  with  the  tuberculous,  M.  Sabourin  informs  me,  but  also 


92  The  Liver  of  Dyspeptics. 

with  a  great  number  of  cachectic  individuals,  cancerous,  etc.,  and 
these  also  have  an  alimentary  canal  all  ready  for  the  abnormal 
fermentations.  I  will  not  dwell  upon  this  aspect  of  the  subject ; 
in  order  to  speak  with  assurance,  it  would  be  necessary  to  have  a 
series  of  observations  of  tuberculous  patients  in  which  the  condi- 
tion of  the  digestive  passages  had  been  carefully  studied,  and  by 
means  of  which  we  might  be  able  to  establish  an  evident  relation- 
ship between  the  alterations  of  the  alimentary  canal  and  sclerosis 
of  the  liver. 

What  I  have  just  said  appears  only  as  a  corollary  of  my  thesis, 
and  I  should  be  pleased  if  some  one  else  would  undertake  to  clear 
up  this  uncertain  point  of  the  history  of  hepatic  tuberculosis.  I 
will  besides  repeat  what  I  said  at  the  beginning  :  I  have  here  con- 
sidered only  one  of  the  anatomo-pathological  and  clinical  forms 
of  dyspeptic  cirrhosis.  Perhaps  there  are  others,  as  the  case  of 
KutrefT,  reported  above  (Case  XXVl),  would  lead  us  to  believe. 

Let  this  then  be  taken  as  a  temporary  foundation-stone  upon 
which  may  be  built  either  variants  of  this  type  or  new  forms. 


PART  III. 

Experimentation, 
previous  experiments. 

The  hope,  so  frequently  disappointed,  of  realizing  with  animals 
the  diseases  observed  with  men,  has,  for  forty  years  past,  urged 
physicians  on  in  the  path  of  experimental  pathology.  But,  on 
account  of  the  complexity  of  the  morbid  act,  these  attempts  have 
only  terminated  in  approximations  or  resemblances,  and  only  in  a 
very  few  cases. 

The  defective  material  conditions  which  every  experimenter 
encounters,  the  unfitness  of  the  subjects  which  he  unavoidably 
has  at  his  disposition,  the  choice  and  the  separation  which  he 
is  obliged  to  make  in  pathogenic  causes,  sufficiently  explain  the 
insufficiency  of  the  results  obtained.  This  is  not  a  reason  for 
renouncing  attempts  of  this  kind  which  at  least  may  be  able,  if 
they  do  not  exactly  reahze  our  desiderata,  to  throw  some  light 
upon  the  questions  investigated  and  enable  us  to  comprehend  the 
obscure  genesis  of  our  diseases. 

To  comprehend,  is  in  short  all  that  we  desire  ;  to  see  indistinctly, 
is  now  very  much.  The  affections  of  the  liver,  and  in  particular 
the  cirrhotic  process,  have  already  tempted  the  curiosity  of  many. 
And,  since  alcohol  appeared  to  be  the  principal  cause  of  it,  it  is 
with  alcohol  especially  that  experiments  have  been  made.  I  will 
not  enter  into  the  details  of  the  labors  of  Dahlstrom,  Ruge, 
Duchek,  Lallemand,  Perrin  and  Duroy,  Kremiensky,  Magnan, 
Pupier,  Dujardin-Beaumetz  and  Audige,  Strassman,  Grand- 
maison,  who  have  only  obtained  cellular  lesions  in  the  liver  of 
their  animals,  in  particular  steatosis. 

The  results  of  MM,  Straus  and  Blocq  have  been  more  satis- 
factory ;  they  have  obtained  in  the  portal  spaces,  around  the 
blood  and  biliary  vessels,  a  well-marked  infiltration  of  embryonic 
cells,  especially  about  the  terminal  branches  ;  but  these  lesions 

93 


94  The  Liver  of  Dyspeptics. 

have  not  gone  beyond  the  initial  stage,  embryonic,  of  cirrhosis, 
which  these  authors  qualify  as  annular,  perilobular,  and  mono- 
lobular.  More  recently  Richter  has  gone  over  these  experiments 
and  has  obtained  with  the  rabbit  a  peri-supra-hepatic  cirrhosis. 
We  will  find  in  the  thesis  of  Laffitte  a  criticism  of  all  these  inves- 
tigations. The  latter  author  has  conscientiously  experimented 
upon  thirty-four  rabbits  to  whom  he  has,  for  a  period  of  time 
varying  from  four  days  to  fifteen  months,  given  wine,  alcohol,  and 
absinthe  ;  now  these  animals  have  presented  some  lesions  of  the 
liver  which  have  no  resemblance  to  the  so-called  alcoholic  atrophic 
cirrhosis. 

The  toxic  influence  of  the  alcohol  has  solely  affected  the 
hepatic  cells,  which  eventually  almost  completely  disappear  and 
are  no  longer  represented  except  by  slender  protoplasmic  fila- 
ments with  little  color  and  arranged  in  a  plexus.  The  nucleus 
has  disappeared,  the  enormously  dilated  capillaries  correspond  to 
the  floor  of  this  plexus.  This  final  alteration  evolves  by  little 
islands  which  appear  on  the  sections  in  the  form  of  colorless 
spots. 

The  production  of  these  necrotic  islands  is  due  to  interstitial 
hemorrhages.  The  connective  tissue  is  ordinarily  intact ;  in  some 
exceptional  cases  we  see  a  few  more  embryonic  nuclei  than  in  the 
normal  condition  ;  but  this  slight  irritation  appears  to  be  in  rela- 
tion with  the  deep  lesions  of  the  gastric  mucous  membrane.  In 
fact  LafKtte  has  noticed,  as  Straus  and  Blocq  had  previously  done, 
a  constant  lesion  ;  hypertrophy  of  ;fehe  gastric  wall  and  a  thickened 
mucous  membrane,  congested,  with  or  without  small  superficial 
ulcerations,  with  or  without  punctiform  hemorrhages.  LafHtte 
is  convinced  that,  in  the  pathogeny  of  cirrhosis  of  the  liver,  we 
must  attribute  an  important  part  to  the  alterations  of  the  ali- 
mentary canal.  "  The  condition  of  the  intestine  and  stomach," 
says  he,  "  should  be  carefully  noted  in  all  the  cases  of  sclerotic 
hypertrophy  of  the  hepatic  gland.  The  acute  or  chronic  irrita- 
tions of  the  digestive  mucous  membrane,  by  opening  a  path  for 
the  micro-organisms  in  contact  with  it  or  to  the  poisons  produced 
by  these  bacteria,  may  react  upon  the  liver  and  thus  provoke  a 
lasting  inflammation  of  the  perilobular  spaces." 

Independent  of  alcohol,  experiments  have  been  made  with  but 
few  substances  administered  by  the  mouth :  direct  injection  into 
the  portal  vein  has  been  more  frequently  practised.  M.  Bouchard 
has  shown  that  naphtol  in  solution  in  diluted  alcohol  injected  into 


Personal  Experiments.  95 

the  portal  vein  produces  a  manifest  sclerosis  accompanied  by  a 
fatty  degeneration  of  the  elements  (organites). 

By  injecting  urate  of  soda  and  lactic  acid  into  the  vessels,  M. 
Charrin  has  succeeded  in  giving  rise  to  modifications  especially 
affecting  the  nobler  elements.  "  I  have  obtained  results  analogous 
to  those  of  Pavone,"  says  he,  "  although  with  difficulty,  by  employ- 
ing bacterian  toxins." 

I  do  not  mention  the  angiocholitis  and  peri-angiocholitis  pro- 
duced by  the  introduction  of  microbian  cultures  into  the  biliary 
passages  (Haot,  Gilbert,  and  Dominici,  etc.).  They  are  connected 
with  the  study  of  infections  of  the  liver. 

As  to  tuberculin,  it  does  not  appear,  according  to  the  results 
observed  with  the  patients  treated  with  the  remedy  of  Koch  for 
weeks  and  months,  in  increasing  doses,  that  it  hasany  sclerogenic 
effect  upon  the  liver.  The  guinea-pigs  which  Koch  inoculated 
with  tuberculin  did  not  present  any  tendency  to  hepatic  cirrhosis. 

PERSONAL  EXPERIMENTS. 

For  purposes  of  experimentation,  among  the  poisons  of  the 
alimentary  canal,  I  have  especially  chosen  those  substances  which 
authorities  generally  believe  to  be  most  injurious,  and  those  which, 
by  their  physical  properties  themselves,  would  appear  susceptible 
of  exercising  an  irritant  or  toxic  action  upon  the  liver. 

Thus  I  have  caused  rabbits  to  swallow  butyric,  lactic,  valerianic, 
acetic,  oleic,  palmitic,  stearic,  margaric,  and  oxalic  acids,  aldehyde, 
acetone,  pepper  (reputed  capable  of  producing  cirrhosis),  living 
cultures  of  Bacterium  coli  communis  of  various  ages  and  from  dif- 
ferent sowings,  toxins  of  this  microbe  prepared  from  recent  cul- 
tures or  from  those  of  more  or  less  age ;  lastly,  some  extract  of 
faeces.  As  a  subject  of  experimentation  I  have  selected  the  rab- 
bit, which  is  easily  handled,  of  which  quite  a  large  number  can  be 
accommodated  in  a  laboratory,  and  of  which  the  liver  readily 
becomes  sclerosed  from  causes  already  known  (psorospermosis, 
biliary  infections,  etc.) ;  besides,  it  is  this  animal  in  particular 
which  has  already  served  for  the  experiments  with  alcohol. 

The  rabbits,  each  occupying  a  separate  cage  and  well  cared  for, 
were  housed  in  quite  a  spacious  room  contiguous  to  the  laboratory, 
well  ventilated,  well  illuminated  and  heated  in  winter.  Their 
ordinary  food  has  consisted  of  cabbage,  carrots,  potatoes,  salad,  etc. 
Each  animal  received  every  morning,  in  a  Petri  box  or  in  a  little 


96  The  Liver  of  Dyspeptics. 

crystallizing  dish,  a  ration  of  bran  soaked  with  the  substance  the 
subject  of  experiment.  The  solid  substances  (fatty  acids)  were 
dissolved  in  ether,  poured  upon  the  bran,  and  the  ether  evaporated  ; 
the  pepper,  ground  fresh  every  morning,  was  also  mixed  with  the 
bran. 

The  animal  only  received  some  other  food  after  it  had  swal- 
lowed this  first  breakfast.  The  rabbits  made  no  objections  to 
taking  the  majority  of  these  substances.  Valerianic  acid,  of 
which  the  odor  is  so  penetrating  and  so  disagreeable,  was  never- 
theless swallowed  after  a  few  days.  The  greatest  difficulty  was 
experienced  in  making  the  rabbits  take  the  acetic  acid.  Two 
however  resigned  themselves  to  eating  their  bran  sprinkled  with 
this  substance. 

In  no  case  was  a  gastric  tube  employed,  for,  as  Laffitte  says, 
we  may  easily  make  a  false  passage  and  pour  the  liquid  into  the 
trachea  ;  a  very  serious  affair,  as  we  may  thus  determine  gastric 
lesions,  so  to  speak,  traumatic,  which  it  is  exceedingly  important 
to  avoid.  The  rabbits  were  weighed  when  the  experiments  com- 
menced and  weekly  afterwards. 

About  sixty  rabbits  were  experimented  upon,  but  a  certain 
number  died  of  tuberculosis  or  refused  to  swallow  the  bran  sprin- 
kled with  the  substance  under  experiment.  Forty-three  have 
given  the  results  here  recorded.  The  animals  were  divided  into 
two  series :  the  first  took  the  substance  employed  in  the  experi- 
ment without  any  addition  ;  the  second,  the  same  substance  with 
10  or  20  c.c.  of  95  percent,  alcohol.  Some  of  these  experiments 
have  lasted  more  than  a  year. 

CHEMICAL   SUBSTANCES. 
Experiment   i. 

Butyric  Acid  alone. — Duration  .•  two  months,  twenty-eight 
days. — Rabbit  weighing  i960  grams,  healthy,  takes  every  day, 
commencing  May  4,  1893,  half  a  gram  of  butyric  acid  with 
which  the  bran  was  sprinkled.  May  9th,  he  no  longer  has 
any  appetite  and  only  weighs  1785  grams.  May  19th  he  eats 
a  little  better  and  weighs  17 10  grams. 

May  24th,  he  eats  perfectly  well,  but  he  continues  to  grow 
thin:  weight,  1580  grams.  He  is  timid  and  keeps  in  the  back 
part  of  his  cage.  June  1st,  the  urine  drawn  with  a  catheter  is 
alkaline,  thick ;  with   the  microscope  we  only  see  some  .white 


PL.  II, 


Fia.l. 


^vi    _.i^,^ 


^•^:;:it'' 


*#%ftlf%:|^^?^ 


-•if 


m 


^1. 


'i^^M 


Fia.2, 


Gj] Jet  del 


Imp.Lemeroier 


Paris. 


Nicolet  Jilh. 


PLATE  II. 

Fig.   I  (Leitz,  oc.  3,  objec.  i). — Liver  of  the  rabbit  of  first  ExrERiMENT. 

The  liver  is  completely  disarranged  {boulevcrse)  by  the  proliferated  connective 
tissue.  On  the  surface,  the  sclerosed  tissue  is  more  abundant  than  the  hepatic.  The 
cirrhosis  is  solely  porto-biliary  ;  the  central  vein  of  the  lobule  is  unatfected.  Tlie 
patches  of  sclerosis  are  united  and  tend  to  completely  isolate  the  lobules  ;  this  isolation 
is  plainly  manifested  in  the  lower  portion  of  the  figure. 

Fig.  2  (Leitz,  oc.  i,  objec.  4). 

A  point  of  Figure  l  greatly  enlarged,  showing  a  sclerosed  portal  space  with  adult 
connective  tissue,  embryonic  cells,  and  slight  proliferation  of  the  biliary  canaliculi.  In 
the  center,  a  little  island  of  hepatic  cells  encompassed  by  the  sclerosis. 


Personal  Experiments.  97 

globules;    it    contains   a  little  albumin,  no  urobilin.     On  June 
14th,  he  only  weighs  1365  grams.     The  urine  is  normal. 

However  he  gains  in  weight  the  next  few  days  and  weighs  1640 
grams  on  June  2 1  St.  He  eats  well  and  appears  to  be  regaining 
his  health.  On  June  26th,  the  daily  dose  of  butyric  acid  was  raised 
to  2  grams.  Starting  from  this  date,  the  rabbit  constantly  dimin- 
ished in  weight  and  died  Aug.  2d,  weighing  only  1195  grams. 

A  iitopsy. 

Liver  weighs  47  grams.  It  is  light  brown  and  marbled  with 
whitish  spots  of  various  dimensions,  communicating  with  each 
other  more  or  less  and  somewhat  below  the  surface  of  the  organ, 
like  depressed  cicatrices.  It  is  very  hard  on  section  and  the  in- 
terior of  the  liver  presents  the  same  appearance  as  the  surface. 
Stomach  covered  with  a  thick  layer  of  mucus  ;  this  removed,  we 
notice  that  the  mucous  membrane  is  swollen  and  strewn  with 
little  ecchymoses  ;  there  is  no  ulceration.  Nothing  particular  in 
the  other  organs.  The  urine  collected  in  the  bladder  is  very  acidy 
and  contains  quite  a  large  percentage  of  albumin  but  no  urobilin. 

Microscopic  Examination  of  the  Liver  (PI.  II,  Figs.  I  and  2). 
— With  a  slight  enlargement  (obj.  i,  ocul.  i  of  Leitz),  we  can  make 
out  that  the  liver  is  literally  turned  topsy-turvy  (bouleverse).  The 
connective  tissue  takes  up  at  least  as  much  space  if  not  more  than 
the  tissue  proper  of  the  organ.  There  is  no  order  in  its  distribution. 

The  patches  of  sclerosis,  rounded,  sinuous,  of  every  shape, 
furrow  the  parenchyma  in  every  direction,  to  the  extent  of  most 
frequently  rendering  the  lobules  unrecognizable.  Some  cellular 
groups,  lobules  or  portions  of  lobules,  are  encompassed  and  en- 
closed in  the  connective-tissue  gangue. 

In  various  places  this  is  perforated  by  the  gaping  mouths  of 
the  vessels.  This  is  perfectly  apparent  to  the  naked  eye.  On 
the  sections  stained  with  picro-carmine  in  particular,  the  bright- 
red  color  of  the  connective  tissue  contrasts  very  plainly  with  the 
reddish-yellow  color  of  the  parenchyma. 

With  a  greater  enlargement  (obj.  4,  ocul.  i  of  Leitz),  we  make 
out  that  the  prohferation  of  connective  tissue  has  the  portal 
spaces  for  its  point  of  departure.  At  these  points  we  see  the 
blood-vessels,  whose  walls  are  completely  blended  with  the  sur- 
rounding tissue,  encompassed  with  concentric  zones  of  adult 
connective-tissue  fibres. 

In  this  respect  it  is  the  same  with  the  biliary  canals ;  from  one 
7 


98  The  Liver  of  Dyspeptics. 

vessel  to  another  the  zones  of  sclerosis  are  merged  with  each 
other,  and  we  have  large  spaces  solely  formed  of  close  and  homo- 
geneous fibrous  tissue.  Here  and  there,  and  principally  in  the 
corners  formed  by  the  approximation  of  two  lobules,  in  the  vicin- 
ity of  the  hepatic  cells,  we  see  a  moderate  number  of  newly  formed 
biliary  canaliculi.  Likewise  at  these  points  there  is  a  very  marked 
infiltration  of  embryonic  cells  and  free  diapedesis  of  leucocytes. 
The  epithelium  which  lines  the  biliary  canals  of  a  certain  calibre 
is  most  frequently  respected  ;  the  lumen  of  these  canals  is  no- 
wise obstructed  and  the  epithelium  has  not  proliferated ;  it  has 
also  lost  nothing  of  its  distinctness.  The  supra-hepatic  veins  are 
generally  unaffected  ;  some,  however,  have  one  wall  slightly 
thickened. 

The  cells  quite  clearly  limit  the  sclerotic  patches,  but  are,  how- 
ever, invaded  at  the  point  of  contact  by  an  embryonic  infiltration. 
The  cellular  spaces  present  their  ordinary  arrangement.  With  a 
very  great  enlargement  (objec.  7,  ocul.  i  of  Leitz),  we  can  see 
that  there  are  very  different  degrees  of  alteration  of  the  cells. 
None  of  them  is  absolutely  normal.  The  least  diseased  have  yet 
quite  a  clear  contour,  but  the  protoplasm  is  slightly  granular. 

Some  have  two  nuclei.  At  a  more  advanced  degree,  the 
granular  degeneration  is  accentuated,  the  contours  of  the  cells 
blend  with  each  other,  and  the  protoplasm  of  all  the  cells  forms  a 
continuous  granular  background.  At  a  yet  more  advanced  stage, 
there  is  some  vitreous  degeneration  and  frequently  a  disap- 
pearance of  the  protoplasm ;  so  that  at  certain  points  we  have 
some  lobules  or  portions  of  lobules  which  present  numerous 
lacunse  throughout  their  whole  extent ;  the  whole  resembles  a 
reticulum  with  quite  large  meshes,  formed  by  the  granular  or 
vitreous  protoplasm  of  the  cells  which  have  not  yet  disappeared. 
There  was  no  fat.  This  examination  leads  to  the  conclusion 
that  we  have  here  a  type,  so  to  speak  perfect,  of  the  atrophic  cirrhosis 

of  Laennec. 

Experiment  ii. 

Butyric  Acid  alone. — Duration  :  two  months,  fourteen 
days. — Rabbit,  of  1855  grams,  healthy,  takes  every  day,  beginning 
May  4,  1893,  half  a  gram  of  butyric  acid.  On  May  9th,  the  appe- 
tite is  moderate  and  the  weight  has  fallen  to  1695  grams.  May 
i6th,  he  eats  a  little  better  and  weighs  1590  grams.  Until  the 
end  he  constantly  loses  weight,  save  a  slight  increase  of  75  grams 
from  the  14th  to  the  2Tst  of  June. 


Personal  Experiments.  99 

On  June  1st,  the  urine,  drawn  with  a  catheter,  contained 
neither  albumin  nor  sugar,  but  with  the  spectroscope  plainly  gave 
the  spectrum  of  urobilin.  June  14th,  it  was  normal.  On  June 
26th,  the  daily  dose  of  butyric  acid  was  raised  to  2  grams.  He 
died  July  i8th,  weighing  only  1165  grams. 

Aiitopsy. 

The  liver  weighs  34  grams.  Absolutely  comparable  to  the 
liver  of  Experiment  I.  The  stomach  is  covered  with  mucus,  but 
presents  no  ecchymoses.  The  kidneys  are  small,  but  do  not  appear 
altered.  Nothing  particular  in  the  other  organs.  The  ttrine  col- 
lected in  the  bladder  is  very  acid  and  contains  albumin  in  large 
quantity.     It  is  light-colored  and  limpid. 

Microscopical  Examination  of  the  Liver. — As  in  Experiment  I, 
there  is  a  true  cirrhosis  :  the  total  surface  of  connective  tissue  is 
perhaps  a  little  less.  All  the  other  details  are  absolutely  com- 
parable. 

Experiment  hi. 

Butyric  Acid  and  Alcohol. — Duration :  sixteen  days. — 
Rabbit  of  1785  grams,  a  little  thin,  takes  every  day,  beginning 
May  4,  1893,  50  centigrams  of  butyric  acid  and  10  c.c.  of  95  per 
cent,  alcohol.  While  diminishing  in  weight  (1610  grams  May 
9th),  he  eats  well  until  May  i6th;  he,  however,  only  weighs  1290 
grams  ;  he  is  depressed  ;  his  ears  have  a  tendency  to  droop.  He 
died  May  20th,  weighing  1050  grams. 

A  utopsy. 

Liver  weighs  34  grams.  Same  color,  same  appearance,  same 
consistence  as  in  Experiments  I  and  II.  Stomach  filled  with  bran. 
No  odor  of  butyric  acid  or  alcohol.  Thick  and  continuous  layer 
of  mucus  upon  the  surface  of  the  mucous  membrane  of  the 
stomach,  which  presents  slight  ecchymotic  arborizations.  Nothing 
particular  in  the  other  organs.     No  urine. 

Microscopic  Exam-ination  of  the  Liver. — Results  comparable 
to  those  of  Experiments  I  and  II,  but  very  much  less  connective 
tissue  ;  embryonic  infiltration  is  more  pronounced. 

Experiment  iv. 

Butyric  Acid  and  Alcohol. — Duration  :  twenty-one  days. — 
Rabbit  of  1685  grams,  not  very  lively,  takes  every  day,  beginning 


lOO  The  Liver  of  Dyspeptics. 

May  21,  1893,  half  a  gram  of  butyric  acid  and  10  c.c.  of  95  per 
cent,  alcohol.  The  urine,  drawn  with  the  catheter  June  Tst,  Avas 
of  normal  composition.  He  died  June  loth,  weighing  only  1070 
grams. 

A  utopsy. 

Liver  weighs  32  grams.  It  is  violet-red  and  very  much  con- 
gested :  there  is  a  goodly  number  of  whitish  spots  marbling  the 
parenchyma.  The  stomach  is  small,  contracted  ;  there  is  neither 
vascularization  nor  ulceration.  The  kidneys  are  small  and  con- 
gested. They  unfortunately  have  not  been  preserved.  The 
bladder  is  very  much  distended.  The  urine  which  it  contains  is 
very  acid  and  of  a  blood-red  color.  Under  the  microscope, 
numerous  red  and  some  white  globules.  Albumin  in  abundance. 
Nothing  particular  in  the  other  organs. 

Microscopical  Examination  of  the  Liver. — Same  degree  of 
sclerosis  of  the  liver  as  in  Experiment  III. 

Experiment  v. 

Butyric  Acid  and  Alcohol. — Duration:  eight  months^ 
fifteen  days. — Rabbit  of  1920  grams,  healthy,  swallows  every  day, 
beginning  August  5,  1893,  2  c.c.  of  butyric  acid  and  20  c.c.  of  95 
per  cent,  alcohol.  The  weight  diminished  in  the  first  place  to 
1570  grams;  from  the  12th  of  August  it  gradually  increased,  and 
May  22,  1894,  the  animal  weighed  2600  grams.  At  this  date  it 
was  killed  by  the  introduction  of  air  into  its  veins. 

Autopsy. 

Liver  weighs  112  grams.  Normal  consistence  and  coloration. 
Alimentary  <:a««/ presents  no  appreciable  alteration  to  the  naked 
eye;  the  mucous  membrane  of  the  stomach  is  a  trifle  more  vascu- 
lar than  normal.     Other  organs  healthy.     No  urine. 

Microscopical  Examination  of  the  Liver. —  Upon  a  section 
stained  with  picro-carmine,  we  notice  that  the  cells  are  markedly 
increased  in  size  and  in  a  state  of  fatty  degeneration.  Their 
arrangement  is  abnormal.  The  protoplasm  is  scarcely  colored, 
and  there  are  some  nuclei  in  almost  the  same  condition. 

In  the  portal  spaces  we  discern  a  fibrous  radiation  hardly 
distinguishable  from  the  cells.  We  ask  oiirselves  if  there  is  not  a 
transformation  of  the  cells  into  fibrous   tissue.      Upon   another 


Personal  Experiments.  i  o  i 

section,  stained  with  carmine  and  hematoxylin,  we  see  some 
spaces  which  have  a  tendency  to  merge  with  each  other  and  to 
circumscribe  the  lobules  with  lines  of  embryonic  cells. 

Experiment  vi. 

Butyric  Acid  and  Alcohol. — Duration :  eleven  months, 
eight  days. — Rabbit  of  2045  grams,  very  vigorous,  takes  every 
day,  beginning  June  14,  1893,  half  a  gram  of  butyric  acid  and  10 
c.c.  of  95  per  cent,  alcohol.  At  first  he  increases  in  weight.  June 
24th,  he  weighed  2100  grams.  The  urine  is  normal.  June  26th, 
we  raise  to  2  grams  the  dose  of  butyric  acid  and  to  20  c.c.  that  of 
alcohol.  The  animal  gradually  grew  thin  until  on  July  5th  it  only 
weighed  1560  grams. 

Then,  with  some  oscillations,  he  gained  and  weighed  2040 
grams  on  September  i6th.  During  two  and  a  half  months  he 
oscillated  between  1850  and  2150  grams.  Starting  from  this  time 
he  constantly  increased  in  weight  up  to  2750  grams  on  May  22, 
1894,  when  he  was  sacrificed  by  the  injection  of  air  into  his  veins. 

A  utopsy. 

Liver  weighs  82  grams,  the  animal  being  killed  at  the  acme  of 
digestion.  The  organ  is  of  normal  consistence  and  color.  All  the 
other  organs  are  healthy,  including  the  stomach. 

Microscopical  Examination  of  the  Liver. — Simple  embryonic 
infiltration,  quite  marked,  however,  of  the  portal  spaces,  but  the 
tissue  has  no  tendency  to  run  between  the  lobules.  The  cells  are 
markedly  affected  and  almost  all  are  in  a  very  pronounced  state  of 
granular  fatty  degeneration. 

Experiment  vii. 

Lactic  Acid. — Duration:  three  months. — Rabbit  of  1850 
grams,  healthy,  takes  every  day,  commencing  April  28,  1893,  2 
grams  of  lactic  acid.  Although  eating  heartily,  he  constantly 
grew  thin  until  May  24th,  when  he  weighed  1350  grams.  Urine 
normal.  He  afterwards  gained  in  flesh,  and,  June  21st,  weighed 
2020  grams.  On  June  26th,  we  increased  to  6  grams  the  dose  of 
lactic  acid ;  two  days  after,  the  animal  had  already  lost  lOO  grams. 
On  July  1st,  we  diminished  the  dose  one  half  because  the  rabbit 
had  refused  his  food  the  day  before.  He  eats  the  bran  with  3 
grams  of  lactic  acid.  He  became  more  and  more  emaciated  and 
died  July  29th,  weighing  only  1230  grams. 


I02  The  Liver  of  Dyspeptics. 

A  utopsy. 

Liver  weighs  19.50  gr.  Mahogany-brown  color  ;  marbled  ap- 
pearance like  the  liver  of  Experiments  I,  II,  III,  and  IV,  with 
butyric  acid.  Same  appearance  upon  section.  The  stomach  ap- 
pears absolutely  normal.  The  kidneys  are  very  small  and  pale. 
Urine  light-colored  ;  neither  sugar  nor  albumin. 

Microscopic  Examination  of  the  Liver. — The  sclerosed  tissue,, 
while  sufficiently  extensive  to  form  large  patches  at  certain  points, 
is,  however,  less  pronounced  than  in  the  butyric  livers  ;  but  there 
is  not  a  portal  space  which  is  not  richly  infiltrated  with  embryonic 
cells  invading  more  or  less  the  adjacent  lobules.  The  cells  are 
little  altered. 

Experiment  viii. 

Lactic  Acid  and  Alcohol. — Duration :  one  year,  twenty- 
four  days. — Rabbit  of  1735  grams,  healthy,  takes,  commencing 
April  28,  1893,  2  grams  of  lactic  acid  and  10  c.c.  95  per  cent,  alco- 
hol daily.  Although  eating  well,  in  the  first  place  he  lost  flesh  until 
May  i6th,  when  he  weighed  1470  grams.  He  afterwards  gained 
until  June  21st,  when  he  weighed  1880  grams.  The  urine  was 
normal.  On  June  26th,  we  began  to  give  him  6  grams  of  lactic 
acid  and  20  c.c.  alcohol  daily.  By  July  5th,  his  weight  had  been 
reduced  to  1830  grams.  Starting  from  this  time,  he  commenced 
to  gain.  From  July  nth  (2020  grams)  to  October  31st  (2140 
grams),  oscillations  around  2000  with  minimum  of  1890  grams 
August  I2th.  From  the  31st  of  October,  1893,  to  the  22d  of 
May,  1894,  gradual  increase  to  2950  grams.  On  this  day  he  was 
killed  by  the  injection  of  air  into  a  vein  of  the  ear. 

Autopsy. 

Liver  weighs  90  grams.  Consistence  and  color  normal.  All 
the  other  organs  normal,  including  the  stomach. 

Microscopic  Exaininatio7t  of  the  Liver. — All  the  portal  spaces 
are  more  or  less  infiltrated  with  embryonic  cells ;  in  some  the  scle- 
rosis stands  out  in  bold  relief,  but  the  cells  are  principally  altered. 
Fatty  degeneratio7t  is  general ;  in  many  of  the  cells  the  nucleus, 
itself  has  disappeared  ;  we  find  fat  vesicles  in  great  number. 
Some  cells  are  enormous,  with  a  very  large  nucleus ;  the  proto- 
plasm and  nuclei  are  scarcely  stained  by  the  carmine  and  hema- 
toxylin. There  is  some  effusion  of  blood  between  the  cellular 
spaces. 


Personal  Experiments.  103 

Experiment  ix. 

Valerianic  Acid  alone. — Duration  :  seven  months,  twenty- 
six  days. — Rabbit  of  1640  grams,  healthy,  takes  daily,  commenc- 
ing May  15,  1893,  half  a  gram  of  valerianic  acid.  In  the  first 
place  there  was  some  trouble  in  making  him  take  the  mixture, 
but  afterwards  he  ate  well.  At  first  he  grew  thin  and  only  weighed 
1385  grams  on  the  14th  of  June.  He  afterwards  gained  and 
weighed  on  June  21st,  1555  grams. 

On  the  26th  of  June  we  commenced  giving  him  2  grams  of 
the  acid  ;  on  this  day  he  weighed  1590  grams  ;  but  starting  from 
this  day,  he  diminished  in  weight,  and  after  some  oscillations  be- 
tween 1200  and  1300  grams,  he  died,  January  11,  1894,  during  the 
night,  only  weighing  11 35  grams. 

Autopsy. 

Liver  weighs  35  grams;  it  is  very  much  congested,  firm  ;  we 
see  no  contractile  tissue  at  the  surface  or  upon  section.  The 
lu7igs  are  congested.  The  stotnach  is  red,  but  there  are  no  ecchy- 
moses  or  ulcerations.  The  kidneys  are  large  and  pale.  The  urine 
neutral,  containing  neither  sugar  nor  albumin. 

Microscopical  Exaininatio?i  of  the  Liver. — Infiltration  evident, 
but  moderate,  of  the  portal  spaces  ;  in  some,  fibrous  tissue.  AH 
the  cells  in  a  state  of  granular  fatty  degeneration  ;  the  nuclei  are 
fairly  well  stained  ;  lacunae  here  and  there,  some  cells  having 
completely  disappeared. 

Experiment  x. 

Valerianic  Acid  alone, — Duration  :  one  month,  eighteen 
days. — Healthy  rabbit  of  1850  grams  takes  every  day,  commencing 
May  30,  1893,  half  a  gram  of  valerianic  acid.  June  6th,  he  weighs 
1890  grams,  but  starting  from  this  date  he  grew  thinner  and  fell 
to  1585  grams  on  June  21st.  On  the  26th  of  June,  we  increased 
the  amount  of  acid  to  2  grams.  The  animal  continued  to  grow 
thin,  and  died  on  July  26th,  weighing  only  995  grams. 

Autopsy. 

Liver  weighs  40  grams.  Mahogany-brown  color,  with  the  ap- 
pearance of  Experiment  Vlll.  The  stomach  is  congested,  but 
MHthout  ecchymoses  or  ulcerations.  The  kidneys  are  large  and 
pale.  The  urine  is  very  acid,  and  contains  albumin  in  appreciable 
quantity. 


I04  The  Liver  of  Dyspeptics. 

Microscopic  Exaininaiio7i  of  the  Liver. — Very  pronounced  scle- 
rosis of  a  goodly  number  of  portal  spaces  ;  others  are  less  scle- 
rosed ;  the  remaining  spaces  are  infiltrated  with  embryotic  cells. 
The  hepatic  cells  are  in  quite  an  advanced  state  of  fatty  degenera- 
tion, but  less  diseased  however  than  in  the  liver  of  Experiment  VIII. 

Experiment  xi. 

Valerianic  Acid  alone. — Duration  :  one  month,  nine  days. 
— Very  vigorous  rabbit,  weighing  2530  grams,  commencing  April 
19,  1893,  takes  daily  half  a  gram  of  valerianic  acid.  He  made 
some  objections  at  first,  but  afterwards  became  accustomed  to  the 
diet.  He  rapidly  grew  thin,  although  eating  very  well ;  he  is  less 
lively  than  at  the  beginning  of  the  experiment.  On  the  28th  of 
July,  he  died,  weighing  only  1560  grams. 

Autopsy. 

Liver  weighs  41  grams.  Absolutely  comparable  to  the  pre- 
ceding one.  The  stomach  is  very  much  thickened  and  corrugated, 
shrunken  towards  the  oesophagus  ;  the  mucous  membrane  is  red, 
in  the  oesophageal  region  especially,  but  presents  neither  ecchy- 
moses  nor  ulcerations.  Lungs  congested.  Kidneys  large  and  pale. 
No  urine. 

Microscopic  Examination  of  the  Liver. — Embryonic  infiltration 
of  all  the  portal  spaces  with  tendency  to  surround  the  lobules 
(annular  cirrhosis).  Cells  in  a  condition  of  granular  fatty  degen- 
eration, sometimes  very  advanced  ;  the  majority  of  the  nuclei  are, 
however,  quite  well  stained. 

Experiment  xii. 

Valerianic  Acid  alone. — Duration :  eighteen  days. — Rabbit 
of  1620  grams,  puny,  takes  every  day,  commencing  April  19,  1893, 
half  a  gram  of  valerianic  acid.  The  first  few  days  he  objected  to 
swallowing  the  bran  sprinkled  with  the  acid,  undoubtedly  on  ac- 
count of  the  odor.  However,  at  the  end  of  a  few  days  there  was 
no  difficulty.  He  rapidly  grew  thin  and  died  May  7th,  weighing 
950  grams. 

Autopsy. 

Liver  small,  weighs  37.50  grams  ;  reddish-brown  ;  hard  upon 
section;  shows  some  patches  comparable  to  those  of  the  butyric 


Personal  Experiments.  1 05 

acid  livers,  but  of  very  much  darker  color,  much  less  clearly  out- 
lined upon  the  rest  of  the  parenchyma,  and  less  confluent.  The 
spleen  is  very  small.  The  Imigs  are  very  much  congested. 
The  stomach  has  a  strong  smell  of  valerianic  acid  ;  its  walls  are 
little  thickened  ;  there  are  neither  ecchymoses  nor  ulcerations. 
Kidneys,  large  and  pale.     No  iirine. 

Microscopic  Examination  of  the  Liver. — Some  portal  spaces  are 
plainly  sclerosed ;  others  are  infiltrated  with  young  cells.  The 
hepatic  cells  are  commencing  to  undergo  fatty  degeneration  with 
contraction. 

Experiment  xiii. 

Valerianic  Acid  and  Alcohol, — Duration:  one  year,  nine- 
teen days. — Rabbit  of  2070  grams,  robust,  takes  daily,  commenc- 
ing May  3,  1893,  half  a  gram  of  valerianic  acid  and  10  c.c.  of  95 
per  cent  alcohol.  He  made  no  objections  to  the  mixture.  He 
immediately  began  to  grow  thin  and  only  weighed  1670  grams  on 
the  16th  of  May. 

He  afterwards  gained,  and  weighed,  on  June  2 1st,  2050  grams. 
On  June  26th,  we  increased  the  amount  of  valerianic  acid  to  2 
grams  and  that  of  alcohol  to  20  c.c.  Fresh  fall  in  weight  until 
July  5th,  when  the  animal  weighed  1770  grams.  Then  he  gained, 
and  after  some  fluctuations  in  weight,  positively  grew  fat.  He 
was  killed  May  22,  1894,  by  the  injection  of  air  into  the  veins; 
weight,  3100  grams. 

A  utopsy. 

Liver  weighs  100  grams.  Color  and  consistence  normal.  All 
the  other  organs  sound. 

Microscopic  Examination  of  the  Liver. — Very  slight  embryonic 
infiltration  of  the  portal  spaces.  Very  advanced  granular  fatty 
degeneration  of  the  hepatic  ceils  ;  many  have  entirely  disappeared. 

Experiment   xiv. 

Acetic  Acid  alone. — Duration :  one  month,  six  days. — Rab- 
bit of  1580  grams,  healthy.  We  mix  with  the  bran  5  c.c.  of  labor- 
atory acetic  acid.  It  is  only  with  dif^culty  that  we  succeed  in 
making  the  rabbit  take  this  mixture;  he  only  concludes  to  eat  it 
when  forced  by  hunger.  At  the  time  that  he  eats  it,  the  bran  has 
yet  a  strong  odor  of  acetic  acid.     He  only  finally  accustoms  him- 


io6  The  Liver  of  Dyspeptics. 

self  to  this  alimentation  about  June  15th.  On  the  14th,  he 
weighed  1550  grams;  the  21st,  1670  grams.  Starting  from  this 
time,  he  quickly  lost  flesh  and  died  July  5th,  weighing  only  1040 
grams. 

Autopsy. 

Liver  weighs  35  grams.  Mahogany-brown,  with  some  con- 
tracted portions.  Very  hard  on  section.  Stomach  red,  but  with- 
out ecchymoses  or  ulcerations.  Nothing  particular  in  the  other 
organs.     Urijie  very  acid,  containing  albumin. 

Microscopical  Examination  of  the  Liver. — Large  bands  and 
patches  of  sclerosis  as  in  the  butyric  livers.  The  cells  are 
markedly  afTected  by  granular  degeneration.  In  certain  very  ex- 
tensive regions,  the  nuclei  themselves  no  longer  form  anything 
but  a  sort  of  dust  colored  by  the  hematoxylin,  upon  an  amor- 
phous background  stained  rose  color  by  the  eosin. 

Experiment  xv. 

Acetic  Acid  and  Alcohol. — Duration :  twenty-three  days. 
— Rabbit  of  i960  grams,  healthy,  takes  every  day,  commencing 
June  3,  1893,  5  c.c.  of  acetic  acid  and  10  c.c.  of  95  per  cent  alco- 
hol. He  accepts  this  food  at  the  beginning  of  the  third  day. 
He  grew  thin  and  died  the  26th  of  June,  weighing  1480  grams. 
He  had  a  large  belly. 

Autopsy. 

Liver  weighs  42  grams.  Reddish-brown  coloration  with  some 
light  spots  moderately  confluent.  Firm  consistence.  Stomach 
distended  and  red,  without  ulceration  or  ecchymoses.  Intestine 
distended.  No  liquid  in  the  peritoneum.  Kidneys  pale.  Urine 
limpid,  very  acid  with  some  albumin. 

Microscopical  Examination  of  the  Liver. — Alterations  much  less 
pornounced  than  in  the  preceding  case.  All  the  portal  spaces  are 
either  moderately  sclerosed  or  infiltrated  to  a  great  extent  with 
embryonic  cells.  The  cells  are  in  a  condition  of  commencing 
granular  degeneration ;  their  nuclei,  however,  are  quite  well 
stained. 

Experiment  xvi. 

Fatty  Acids. — Duration  :  eight  months,  twenty-six  days. — 
Vigorous  rabbit  of  1780  grams,  commencing  May  4,   1893,  takes 


Personal  Experiments.  107 

every  day  half  a  gram  of  oleic  acid  and  as  much  palmitic  acid. 
The  acids  are  dissolved  in  ether  and  the  solution  poured  upon  the 
bran  and  allowed  to  evaporate.  After  losing  weight  until  May 
i6th  (1580  grams),  the  animal  gained  in  flesh  and  on  June  21st, 
weighed  1950  grams. 

Commencing  June  26th,  2  grams  of  each  of  the  following  sub- 
stances were  daily  ingested : 

Oleic  acid 
Palmitic  acid 
Margaric  acid 
Stearic  acid. 

There  was  again  a  loss  of  weight  and  on  July  5th  the  animal 
weighed  1655  grams.  From  this  time  on  there  was  an  increase 
until  September  i6th,  when  his  weight  was  1910  grams.  He  only 
attained  the  weight  of  1950  grams  after  having  become  accustomed 
to  the  first  doses  of  acid.  He  has  always  had  a  good  appetite 
and  his  ration  of  fresh  vegetables  has  frequently  exceeded  that  of 
the  other  animals.  From  October  loth  to  December  17th,  his 
weight  oscillated  between  1800  and  i860  grams.  About  the  end  of 
December,  the  animal  commenced  to  grow  thin  ;  January  9,  1894, 
he  weighed  only  1400  grams  and  died,  January  27th,  weighing 
1365  grams. 

A  utopsy. 

Moderate  tuberculosis  of  the  lung.  Liver  weighs  46  grams. 
Grayish  color  ;  a  little  hard  upon  section.  The  alimentary  canal 
presents  no  peculiarity  ;  there  is  no  peritoneal  tuberculosis. 

Microscopical  Examination  of  the  Liver. — Some  solitary  tuber, 
cles  in  the  hepatic  tissue  ;  some  others  along  the  vessels.  No 
other  proliferation  except  a  very  moderate  infiltration  at  some 
few  points  where  two  or  three  tubercles  are  united,  in  the  vicinity 
of  the  portal  spaces.  The  cells  are  very  plainly  in  a  condition  of 
granular  fatty  degeneration. 

Experiment  xvii. 

Fatty  Acids  and  Alcohol. — Duration:  one  year,  sixteen  days. — 
Rabbit  of  1480  grams  daily  takes,  commencing  May  4,  1893,  half 
a  gram  of  oleic  and  as  much  palmitic  acid  dissolved  in  ether  and 
sprinkled  on  the  bran,  and  also  10  c.c.  95  per  cent,  alcohol. 
Weight  stationary  until  May  9th,  when  he  weighed  1496  grams. 


io8  The  Liver  of  Dyspeptics. 

In  the  first  place  he  diminished  a  little  in  weight.  May  24th,  he 
weighs  1340  grams  ;  then  he  increased  in  weight  to  1670  grams. 
Commencing  June  26th,  he  took  until  death  : 

Oleic  acid "] 

Palmitic  acid \    ,    >,  „ 

A/r          •        -J  r  (aa)  2  grams. 

Margaric  acid 

Stearic  acid J 

95  per  cent,  alcohol..  .  .20  c.c. 

Fresh  loss  of  weight ;  the  animal  weighing  1590  grams,  July  5th. 
For  a  month  and  a  half  after,  he  oscillated  in  weight,  and 
weighed,  July  nth,  1760  grams;  July  21st,  1805  grams;  August 
5th,  1740  grams;  August  12th,  1800  grams;  August  26th,  2000 
grams.  From  this  date  he  gradually  gained  in  weight,  notwith- 
standing the  daily  ingestion  of  his  8  grams  of  fatty  acids,  and 
his  20  c.c.  of  alcohol. 

On  the  28th  of  May,  1894,  he  weighed  26CXD  grams.  He  was 
killed  on  this  date  by  the  injection  of  air  into  the  veins.  There 
was  never  any  sugar  or  albumin  in  the  urine,  but  at  several  times 
it  gave  the  characteristic  spectrum  of  urobilin. 

Autopsy. 

Liver  weighs  82  grams.  It  is  remarkably  tri-lobed,  as  if  foli- 
ated. Its  color  was  normal.  All  the  other  organs,  including  the 
stomach,  present  no  alterations. 

Microscopic  Examination  of  the  Liver. — No  trace  of  connective- 
tissue  proliferation.  The  cells  are  in  quite  an  advanced  state  of 
granular  fatty  degeneration.  Here  and  there,  the  trabecular 
arrangement  is  preserved,  but  in  one  space  we  can  no  longer 
distinguish  the  cells  from  each  other  except  by  their  nuclei. 
These  cells  are  either  hypertrophied  to  the  extent  of  touching 
those  of  the  neighboring  space,  or,  on  the  contrary,  diminished 
in  volume,  so  that  the  spaces  are  very  narrow,  with  very  large 
openings  between  them  ;  they  resemble  a  net  with  large  meshes. 
Lastly,  at  certain  points,  in  patches,  the  protoplasm  of  all  the 
cells  is  run  together,  and  the  nuclei,  pale  and  swollen,  stand 
out  on  a  uniform  and  almost  amorphous  background. 

Experiment  xviii. 

Acetone. — Duration:  seven  days. — Rabbit  of  1620  grams 
takes,  commencing  July  19, 1893,  a  daily  dose  of  10  c.c.  of  acetone. 


Personal  Experiments.  109 

He  died  on  July  25th.     His  urine  contained  a  large  amount  of 
albumin. 

A  utopsy. 

Liver  weighs  30  grams ;  it  is  very  much  congested.  The 
kidneys  are  very  large  and  pale.  The  mucous  membrane  of 
the  stomach  is  very  red,  but  there  are  no  ecchymoses  or  ulcera- 
tions. 

Microscopical  Examination  of  the  Liver. — The  cells,  without, 
being  granular,  are  cloudy  ;  there  is  a  lack  of  clearness  of  outline, 
stumped,  so  to  speak.  Around  some  biliary  canals,  there  is  a  thin 
ring  of  sclerosis,  undoubtedly  due  to  a  slight  degree  of  ascending 
angiocholitis,  anterior  to  the  experiment.  Independently  of  this, 
no  proliferation  of  connective  tissue. 

Microscopical  Examination  of  the  Kidneys. — The  cortical  por- 
tion is  very  much  diseased.  All  the  convoluted  tubules  have  their 
epithelia  swollen  to  the  extent  of  closing  up  the  lumen  ;  the  pro- 
toplasm is  granular  or  simply  cloudy  ;  the  nucleus  is  extremely 
pale  even  in  the  hematoxylin  preparations.  Of  the  glomeruli, 
some  have  kept  their  normal  size,  but  in  the  cavity  of  the 
glomerulus  we  find  a  granular  detritus  which  appears  to  be  albu- 
minous; others  are  very  much  swollen,  and  the  cavity  is  obliter- 
ated by  the  contact  of  the  epithelia. 

The  straight  tubes  are  less  affected  ;  the  epithelium  is  scarcely 
swollen  ;  almost  everywhere  they  contain  the  same  granular  de- 
tritus mentioned  above.  In  a  word,  well-marked  epithelial 
nephritis. 

Experiment  xix. 

Acetone. — Duration:  seven  days. — Rabbit  of  2130  grams, 
commencing  July  4,  1893,  takes  daily  10  c.c.  of  acetone.  He  died 
on  the  morning  of  July  nth,  weighing  1530  grams  (he  lost  600 
grams  in  seven  days).  The  zirine,  slightly  acid,  contained  a  large 
amount  of  albumin. 

A  utopsy. 

Liver  weighs  53  grams  ;  it  is  very  much  congested,  violaceous 
in  hue.  The  kidneys,  the  right  one  especially,  are  enormous.  The 
mucous  membrane  of  the  stomach  is  swollen,  red,  and  as  if  pig- 
mented. 

Microscopic  Examination  of  the  Liver  and  Kidneys. — Abso- 
lutely comparable  to  that  of  the  preceding  experiment. 


no  The  Liver  of  Dyspeptics. 

Experiment  xx. 

Acetone. — Duration .-  sixteen  days. — Rabbit  of  1480  grams 
takes  every  day  from  July  19th  to  August  4,  1893,  4  c.c.  of  acetone. 
He  died  on  August  4th.  The  urine,  strongly  acid,  contains  a 
large  amount  of  albumin,  no  sugar.  Under  the  microscope  we 
find  some  red  and  white  globules. 

Autopsy. 

Liver  weighs  21  grams.  An  incident  happened  at  the  begin- 
ning of  the  autopsy  which  prevented  me  from  examining  the 
other  organs,  and  when  I  desired,  some  hours  later,  to  continue 
the  examination,   I    found    that   they  had    been   thrown    away. 

Microscopical  Examination  of  the  Liver. — We  notice  a  certain 
degree  of  embryonic  sclerosis,  as  much  venous  as  biliary,  very 
marked  in  some  portal  spaces. 

The  cells  are  unrecognizable,  entirely  granular,  and  confounded 
with  each  other.  It  is  probable  that  the  kidneys  would  have  pre- 
sented alterations  analogous  to  those  of  the  kidneys  of  the  two 
preceding  animals. 

Experiment  xxi. 

Aldehyde. — Duration  :  six  months,  twenty-three  days. — Rab- 
bit of  2030  grams.  On  June  29,  1893,  some  bran  mixed  with  10 
c.c.  of  aldehyde  was  placed  before  him.  He  refused  this  food  until 
the  15th  of  July,  and  grew  thin  during  this  time,  as  we  gave  him 
very  little  to  eat ;  July  5th,  he  weighed  1770  grams.  On  the  15th 
of  July,  he  decided  to  swallow  his  aldehyde.  His  weight  oscil- 
lated for  six  months,  and  in  a  very  irregular  manner,  between 
1935  and  1 5 10  grams.  He  finally  died  on  January  28,  1894, 
weighing  1345  grams.  His  urine  never  contained  either  sugar  or 
albumin. 

Autopsy. 

Liver  weighs  22  grams  ;  it  is  dark  brown.  The  kidneys  offer 
nothing  particular  to  the  naked  eye.  The  stomach  is  small,  con- 
tracted, thickened  ;  the  mucous  membrane  presents  no  appreciable 
alterations. 

Microscopical  Examination  of  the  Liver. — Moderate  embryonic 
connective-tissue  proliferation  about  some  small  portal  spaces. 
The  cells  are  in  a  very  manifest  condition  of  granular  degenera- 


Personal  Experiments.  ill 

tion  ;  if  we  can  yet  here  and  there  distinguish  the  spaces,  the 
protoplasm  is  distintegrated  and  the  cells  have  lost  their  contour; 
we  find  many  free  granulations. 

Experiment  xxii. 

Oxalic  Acid. — Duration  :  one  month. — Rabbit  of  1905  grams, 
commencing  June  2,  1893,  takes  daily  25  centigrams  of  oxalic 
acid.  He  diminished  in  weight,  and  on  June  14th,  weighed  1755 
grams.  He  then  began  to  gain,  and  reached  1805  grams  on  June 
2 1  St.  Dating  from  the  24th,  we  increased  the  dose  to  i  gram, 
but  the  animal  only  took  part  of  it  and  refused  the  remainder. 
He  nevertheless  grew  thin,  and  died  July  3d,  weighing  1105 
grams.      Urine,  very  acid,  contains  a  little  albumin. 

A  utopsy. 

Liver  weighs  33  grams  ;  it  is  brown.  The  kidneys  are  a  little 
increased  in  size.  There  is  only  some  diffused  redness  of  the 
mucous  membrane  of  the  stomach. 

Histological  Examination  of  the  Liver. — Ascending  angiocholi- 
tis  of  the  large  biliary  trunks,  undoubtedly  consecutive  to  the  gas- 
tro-intestinal  inflammation.  Some  interlobular  veins  in  the  small 
spaces  have  a  ring  of  sclerosis  already  formed  or  some  embryonic 
infiltration.  The  cells  are  completely  degenerated,  disintegrated, 
blended  with  each  other. 

Histological  Examination  of  the  Kidneys. — Cloudy  swelling  of 
the  epithelium  of  the  convoluted  tubules  and  of  the  ascending 
branches  of  Henle. 

Experiment  xxiii. 

Oxalic  Acid. — Duration:  one  month. — Rabbit  of  1700  grams 
takes  daily,  commencing  July  5,  1893,  half  a  gram  of  oxalic  acid. 
He  increased  in  weight  until  July  nth,  when  he  reached  1930 
grams.  From  this  time  he  diminished  in  weight  and  died  Aug. 
4th,  weighing  mo  grams.  Urine,  very  acid,  contains  some 
albumin. 

Autopsy. 

Liver  weighs  40  grams,  reddish-brown.  Kidneys  large  and 
pale. 

Microscopic  Examination  of  Liver  and  Kidneys. — Absolutely 
comparable  to  the  preceding  case. 


112  The  Liver  of  Dyspeptics. 

Experiment  xxiv. 

Pepper  alone. — Duration  :  twenty-seven  days. — Rabbit  of 
1910  grams  eats  every  day,  mixed  with  some  bran,  half  a  gram  of 
pepper  freshly  ground,  commencing  June  6,  1893.  He  rapidly 
grew  thin,  and  died  July  3d,  weighing  1575  grams.  There  was 
no  urine. 

Autopsy. 

Liver  weighs  61  grams ;  it  is  very  much  congested,  violaceous 
in  color.  The  kidneys  are  also  markedly  congested  and  increased 
in  size.  The  stomach  is  distended,  thinned,  but  presents  no  altera- 
tions of  the  mucous  membrane. 

Microscopical  Examination  of  the  Liver. — Well  marked,  fully 
developed  porto-biliary  sclerosis,  with  tendency  to  penetration  of 
the  lobules.  Moderate  formation  of  biliary  canaliculi.  Cells  in  a 
state  of  granular  degeneration. 

Microscopic  Examination  of  the  Kidneys. — Not  an  epithelial 
cell  but  is  swollen  and  granular,  and  in  some  tubes  the  cells  are 
completely  disintegrated.  Embryonic  proliferation  of  the  con- 
nective tissue ;  the  coats  of  the  arteries  are  markedly  thickened. 

Experiment  xxv. 

Pepper  and  Alcohol. — Duration  :  eleven  months,  sixteen 
days. — Rabbit  of  1820  grams  eats  every  day,  commencing  June 
6,  1893,  half  a  gram  of  freshly  ground  pepper  mixed  with  some 
bran,  upon  which  were  sprinkled  10  c.c.  of  alcohol.  At  first  the 
animal  grew  thin,  and  on  June  14th,  weighed  1630  grams.  Then 
he  increased  in  weight  up  to  1870  grams  on  June  21st,  but  he 
again  lost  weight,  the  amount  of  alcohol  having  been  increased  to 
20  c.c.  June  26th.  He  fell  to  1240  grams  August  5th.  From 
this  time  he  gained  and  increased  in  weight  up  to  May  22,  1894, 
when  he  was  killed  by  the  injection  of  air  into  the  veins,  then 
weighing  2550  grams. 

Autopsy. 

Liver  weighs  80  grams.  Coloration  normal.  Nothing  special 
in  the  other  organs. 

Microscopical  Examination  of  the  Liver. — Some  portal  spaces 
with  well  marked  embryonic  infiltration.  The  cells  are  very  much 
affected  by  the  alcohol  and  have  undergone  granular  fatty  de- 
generation, especially  complete  in  the  peripheral  portions  of  the 


Personal  Experiments.  113 

lobules  ;  in  the  vicinity  solely  of  the  central  vein,  Vi'C  find  the 
trabecular  arrangement  yet  preserved,  with  some  cells,  the  proto- 
plasm of  which  still  takes  the  stain,  but  in  an  irregular  manner,  in 
spots.  Everywhere  else  the  cells,  very  pale,  are  completely  dis- 
torted, turned  topsy-turvy,  and  only  present  to  the  eye  a  back- 
ground marbled  with  yellow  and  rose  color  or  a  faint  tint  of 
violet,  upon  which  the  nuclei,  quite  well  preserved,  stand  out  in 
bold  relief. 

LIVING  CULTURES   OF   BACTERIUM   COLI   COMMUNIS. 

Before  experimenting  upon  rabbits  with  intestinal  microbes,  it 
was  proper  that  we  should  know,  from  a  bacteriological  point  of 
view,  what  were  the  contents  of  their  alimentary  canals.  It  was 
natural  to  give  them  cultures  of  such  microbes  as  we  ordinarily 
encounter  with  the  normal  rabbit,  so  as  to  approximate  as  closely 
as  possible  to  that  which  takes  place  with  man  when  there  is  pro- 
duced with  him  an  auto-infection  of  gastro-intestinal  origin. 

It  was  a  sort  of  artificial  auto-infection  which  I  have  endeav- 
ored to  realize  with  the  rabbit.  Now  it  is  the  Bacterium  coli 
which  I  have  invariably  found  in  the  intestinal  canal  of  this  ani- 
mal, most  frequently  in  a  condition  of  purity.  It  is  there  pre- 
sented with  its  most  clearly  marked  characteristics :  pecuHarities 
of  culture,  indol  reaction,  coagulation  of  milk,  fermentation  of 
lactose,  and  very  great  mobility  especially,  which,  as  we  know,  is 
a  guarantee  of  its  vitality  and  virulence.  It  is,  then,  alone  with 
the  Bacterium  coli  that  I  have  experimented,  and  the  Bacterium 
coli  coming  from  the  intestine  of  the  rabbit  itself.  We  took  a 
ball  of  rabbit  dung  as  fresh  as  possible,  cut  it  in  two  with  a 
heated  instrument,  and  from  its  centre  charged  a  platinum  wire 
with  material  to  infect  a  culture  tube  of  bouillon  ;  resowing  in 
another  tube  of  bouillon  and  upon  solid  media  at  the  end  of 
twelve  to  twenty-four  hours.  The  first  culture  was  generally 
pure;  the  second  one  was  always  so.  In  order  to  realize  different 
conditions  of  virulence  and  vitality,  I  gave  cultures  of  different 
ages  to  my  rabbits.  Some  ingested  a  continuous  living  culture, 
that  is,  taken  from  the  same  vessel  in  which  the  original  culture 
was  still  progressing ;  others  took  a  living  twenty-four-hours-old 
culture  from  direct  sowing,  that  is,  a  culture  fresh  and  renewed 
daily.  Lastly,  to  the  remainder  of  the  rabbits  we  administered  a 
living  culture  twenty-four  hours  old  obtained  by  successive  resowings 
daily- 


114  ^^^  Liver  of  Dyspeptics. 

As  an  exception,  one  of  my  animals  ingested  a  culture  of 
Bacterium  coli  obtained  from  the  faeces  of  a  healthy  man. 

Experiment  xxvi. 

Continuous  Living  Culture  of  Bacterium  Coli  Com- 
munis.— Duration  :  twenty-jive  days. — Rabbit  of  1870  grams,  com- 
mencing April  19,  1893,  daily  swallowed  half  a  cubic  centimetre 
of  the  pure  culture  mixed  with  its  bran.  It  rapidly  grew  thin 
and  on  the  morning  of  May  14th,  we  found  it  dead  in  its  cage. 
It  then  weighed  1205  grams. 

Autopsy. 

Liver  weighs  30.5  gr.  The  other  organs  present  no  apparent 
alteration ;  the  mucous  membrane  of  the  stomach  seems  normal. 

Microscopic  Examination  of  the  Liver. — Ascending  angiocholitis 
of  the  large  trunks  with  very  pronounced  biliary  sclerosis ;  in  the 
small  portal  spaces,  slight  embryonic  infiltration  as  much  portal 
as  biliary  ;  no  organized  connective  tissue  as  with  the  large  trunks. 
The  cells  are  very  variously  affected  ;  we  notice  all  degrees  of  cell- 
ular necrosis,  from  simple  cloudiness,  with  or  without  swelling, 
up  to  disintegration  of  the  protoplasm  into  a  substance  which  is 
no  longer  even  granular,  a  sort  of  vitrification,  without  precise 
limit  of  cellular  contour.  Other  cells  are  simply  smaller  or  larger 
than  normal,  without  appreciable  change  of  the  protoplasm.  The 
spaces  are  again  met  with  in  the  vicinity  of  the  central  vein  and 
also,  in  many  lobules,  as  far  as  half  of  the  diameter. 

The  nuclei  are  brightly  stained :  there  were  no  preparations 
made  with  Flemming's  reagent,  so  that  it  was  impossible  to  say 
if  they  were  in  a  condition  of  karyokinesis ;  we  can  simply  pre- 
sume it  from  their  bright  color.  The  cellular  lesions  are  not  pre- 
sented in  the  form  of  circumscribed  islands  but  are  irregularly 
disseminated  :  their  location  however  is  constant ;  they  affect  the 
peripheral  half,  if  not  two  thirds  of  the  lobule. 

Experiment  xxvii. 

Continuous  Living  Culture  of  Bacterium  Coli  Com- 
munis.— DuratioTi :  thirty-five  days. — Guinea-pig  of  290  grams 
daily  ingested,  from  April  19,  1893,  half  a  cubic  centimetre  of 
pure  culture.  We  found  him  dead  on  the  morning  of  May  24th, 
weighing  only  205  grams. 


Personal  Experiments.  115 

A  utopsy. 

Liver  weighs  1 1  grams ;  it  is  of  normal  consistence  and  color. 
The  stomach  is  absolutely  normal,  also  the  intestine.  No  other 
organ  presents  any  apparent  alteration. 

Microscopic  Examination  of  the  Liver. — The  walls  of  the  blood- 
vessels of  a  large  number  of  portal  spaces  are  thickened,  with 
slight  peri-vascular  embryonic  infiltration.  The  alteration  of  the 
cells,  although  less  pronounced  than  in  the  preceding  experiment, 
is  absolutely  analogous. 

Experiment  xxviii. 

Continuous  Liver  Culture  of  Bacterium  Coli  Com- 
munis.— Duration:  twenty-one  days. — Rabbit  of  1765  grams,  com- 
mencing May  20,  1893,  takes  daily  2  c.c.  of  pure  culture.  On 
June  loth,  in  the  evening,  convulsive  phenomena  for  three  hours. 
At  6  P.M.,  the  rectal  temperature  was  36°.  7  C;  at  8  P.M.,  34°.  i  C 
He  died  at  8.30  P.M.     His  weight  was  1220  grams. 

A  utopsy. 

Liver  weighs  41  grams;  of  brownish-red  color;  its  consistence 
seems  normal.  The  stomach  is  a  little  thickened  and  contains  a 
large  quantity  of  mucus.  The  intestine  presents  nothing  abnor- 
mal. The  kidneys  appear  normal  to  the  naked  eye.  The  bladder, 
very  much  distended,  contains  a  colorless,  alkaline  urine,  slightly 
cloudy,  with  a  small  amount  of  albumin.  The  preparations  of 
the  liver  and  kidneys  were  unfortunately  mislaid  and  they  were 
not  examined  microscopically. 

Experiment  xxix. 

Continuous  Living  Culture  of  Bacterium  Coli  Com- 
munis.— Duration  :  one  month,  thirteen  days. — Rabbit  of  1 630 
grams  takes  daily,  commencing  June  15,  1893,  2  c.c.  of  pure  con- 
tinuous culture  of  human  B.  C.  C.  He  died  on  the  28th  of  July, 
weighing  only  1220  grams.  At  3  P.M.,  the  rectal  temperature  was 
36°.  3  C;  at  7  P.M.,  34°.  5  C.     Dead  a  few  moments  after. 

Autopsy. 

Liver  weighs  38.50  gr.  Brown  color.  Nothing  particular  in 
the  other  organs. 


1 16  The  Liver  of  Dyspeptics. 

Microscopic  Examination  of  the  Liver. — Ascending  angiochoHtis 
of  the  large  trunks  and  very  pronounced  biliary  sclerosis  of  the 
large  spaces.  In  the  spaces  of  medium  calibre,  we  clearly  see 
peri-and  endophlebitis  with  obliterating  tendency.  Here  and 
there  we  find  central  hemorrhages,  likewise  simple  congestion,  the 
red  globules  filling  the  inter-trabecular  capillaries  or  rather  the 
spaces  still  remaining  free  between  the  cells,  as  the  intervals  are 
not  always  recognizable.  The  cells  present  alterations  analogous 
to  those  of  Experiment  xxvi. 

Experiment  xxx. 

Living  Culture  24  Hours  Old  from  Direct  Sowing 
WITH  B.  C.  C. — Duration  :  thirteeji  days. — Rabbit  of  1855  grams 
took  daily,  from  May  4,  1893,  half  a  cubic  centimetre  of  pure  cul- 
ture. On  May  i6th,  the  animal  commenced  to  throw  its  head 
backward,  momentarily  being  in  a  condition  of  opisthotonos.  He 
is  very  thin,  weighing  only  1200  grams.  On  May  i6th,  at  9  P.M., 
his  rectal  temperature  was  35°.  4  C.  ;  at  4  A.M.,  34°.  6  C.  He  died 
at  7  A.M.  in  a  condition  of  opisthotonos. 

Autopsy. 

Liver  weighs  28  grams.  Normal  color,  but  the  tissue  is  friable 
and  nowhere  hard  upon  section.  The  mucous  membrane  of  the 
stomach  is  here  and  there  red,  but  not  at  all  ulcerated.  Its  walls 
are  considerably  thickened  beneath  the  mucous  membrane ;  we 
might  call  it  a  neoplastic  infiltration.  The  intestine  presents 
nothing  particular.  The  spleen  is  small.  The  blood  of  the  heart 
contains  some  stumpy  and  mobile  Bacter.  coli. 

Microscopic  Examination  of  the  Liver. — Ascending  angiochoH- 
tis of  the  large  trunks,  but  much  less  marked  than  in  the  preced- 
ing experiments.  No  connective-tissue  proliferation  in  the  portal 
spaces.  The  cells  are  principally  affected.  They  are  reduced  to 
a  sort  of  granular  dust  forming  a  uniform  background  for  the 
nuclei.  Upon  some  preparations  made  with  Kuhn's  blue,  with  an 
immersion  lens,  we  very  well  see  the  vesicular  condition  of  these 
nuclei,  of  which  the  chromatic  substance  is  sometimes  divided  and 
collected  at  the  two  poles,  sometimes  scattered  haphazard  in  the 
nucleus.  At  certain  points  the  trabecular  arrangement  is  still  pre- 
served, but  for  the  nuclei  alone ;  the  cellular  protoplasm  has 
almost  entirely  disappeared  and  the  rows  of  nuclei  form  a  delicate 


Personal  Experiments.  1 17 

network  with  large  meshes  ;  it  would  seem  as  if  there  were  only 
the  skeletons  of  the  cells  still  remaining.  At  the  first  glance,  we 
would  imagine  that  we  were  examining  a  section  of  pulmonary 
tissue. 

Experiment  xxxi. 

Living  Culture  24  Hours  Old  Directly  Infected  with 
B.  C.  C. — Duratiojt :  one  month,  twenty-five  days. — Rabbit  of  1345 
grams,  commencing  May  20,  1893,  daily  takes  i  c.c.  of  pure  cul- 
ture. He  gradually  grew  thin,  and  on  June  21st,  weighed  1185 
grams. 

Shortly  afterwards  we  observed  an  abscess  the  size  of  a  walnut 
on  his  left  flank.  This  opened  externally  on  June  27th,  and  gave 
exit  to  a  thick,  odorless  pus  which  contained  no  micro-organisms, 
a  culture  medium  infected  with  this  pus  remaining  sterile.  Anti- 
septic dressing.  On  the  nth  of  July,  the  animal  weighed  1075 
grams.  July  15th,  he  became  cold,  but  had  no  convulsions  ;  pos- 
sibly he  had  some  the  evening  before  or  during  the  night.  At  8 
A.M.,  the  rectal  temperature  was  35°. 8  C;  at  2  P.M.,  34°.3  C.  The 
animal  died  at  3  P.M.,  weighing  985  grams. 

A  utopsy. 

Liver  weighs  28.50  grams.  Tissue  very  friable.  The  pyloric 
portion  of  the  stomach  is  injected  ;  nothing  abnormal  about  the 
intestine.  The  lungs  are  very  much  congested.  The  kidneys  ap- 
pear normal  to  the  naked  eye. 

Microscopic  Examination  of  the  Liver. — Ascending  angiocholitis 
of  the  large  trunks,  but  without  well-pronounced  sclerosis  ;  in  the 
medium-sized  portal  spaces  a  very  slight  porto-biliary  embryonic 
infiltration.  The  cells,  not  so  much  disintegrated  as  in  the  liver 
of  the  animal  of  the  preceding  experiment,  do  not  the  less  pre- 
sent the  very  profound  alterations  of  granular  degeneration  ;  the 
trabecular  arrangement  is  preserved  at  a  greater  number  of  points. 
The  intra-lobular  congestion  is  very  marked  ;  the  red  globules  of 
the  central  capillaries  of  the  lobule  form  a  large  circular  yellow 
spot  around  the  central  vein. 

Microscopic  Examination  of  the  Kidneys. — There  is  cloudy  swell- 
ing of  all  the  epithelial  cells,  but  the  alteration  is  most  marked  in 
the  convoluted  tubules  ;  there  the  lumen  is  completely  obliterated 
by  the  swollen  cells,  or,  if  this  is  re-established,  it  is  by  the  death 
of  the  whole  central  portion  of  the  degenerated  cell,  the  base 


1 1 8  The  Liver  of  Dyspeptics. 

alone  remaining  with  the  nucleus  and  presenting  an  irregular 
disintegrated  border. 

We  besides  observe  an  intense  capillary  inflammation  with 
commencing  connective-tissue  proliferation. 

Microscopic  Examination  of  the  Limgs. — The  alveoli  were  com- 
pletely filled  with  blood  ;  the  pulmonary  'epithelium  is  in  place, 
but  the  nuclei  are  very  brightly  stained  and  increased  in  size  ;  the 
capillaries  are  gorged  with  blood  and  are  intensely  inflamed  at 
certain  points.     No  other  considerable  alteration. 

Experiment  xxxii. 

Living  Culture  24  Hours  Old — Successive  Resow- 
INGS  OF  B.  C.  C. — Duration:  eighteen  days. — Rabbit  of  1995 
grams,  beginning  May  4,  1893,  daily  takes  half  a  cubic  centimetre 
of  pure  culture.  Every  day  we  re-infected  a  fresh  tube  from  the 
tube  of  the  day  before.  May  9th,  the  rabbit  weighed  1780  grams 
and  the  amount  of  culture  was  increased  to  2  c.c.  May  i6th,  he 
weighed  1405  grams.  We  found  him  dead  on  the  morning  of 
May  22d. 

Autopsy. 

Liver  weighs  65  grams  ;  it  is  congested,  violet-red,  and  of  firm 
consistence.  The  stomacJi,  greatly  distended,  presents  a  thick 
layer  of  mucus  adherent  to  the  mucous  membrane  and  forming  as 
it  were  a  second  pocket  for  the  food.  Very  numerous  ecchymoses 
over  the  whole  surface  of  the  mucous  membrane.  The  intestine 
presents  nothing  abnormal.  The  kidneys  appear  healthy  to  the 
naked  eye.     The  spleen  is  small,  elongated. 

Microscopical  Examination  of  the  Liver. — Ascending  angio- 
cholitis  with  very  marked  sclerosis  of  the  large  trunks. 

In  the  portal  spaces  of  medium  and  small  calibre,  very  plain 
embryonic  connective-tissue  infiltration  ;  some  supra-hepatic  veins 
also  show  commencing  sclerosis.  Very  marked  degeneration  of 
cells  as  in  the  livers  of  the  animals  of  the  preceding  experiments. 

Microscopic  Examinations  of  the  Kidneys. — Same  alterations  as 
in  the  preceding  experiment ;  the  capillary  inflammation  is,  how- 
ever, less  intense. 

Experiment  xxxiii. 

Living  Culture  24  Hours  Old  from  Successive  Re- 
infections  OF  B.    C.    C. — Duration :    one    month,   twe?ity-four 


Personal  Experiments.  119 

days. — Rabbit  of  1605  grams,  beginning  May  23,  1893,  daily 
takes  2  c.c.  of  pure  culture.  He  gradually  grew  thin,  and,  July 
nth,  weighed  1340  grams.  On  July  i6th,  the  animal  became 
cold  :  at  1 1  A.M.,  the  rectal  temperature  was  34°.  6  C;  at  i  P.M. 
33°-9  C.     Death  took  place  at  2  P.M. 

A  utopsy. 

Liver  weighs  25  grams;  it  is  violet-red.  Th.&  stomachy  intes- 
tine, and  kidneys  present  nothing  in  particular  to  the  naked  eye. 
The  spleen  is  large.  The  urine  collected  in  the  bladder  is  pale, 
without  sugar  or  albumin. 

Microscopic  Examination  of  the  Liver. — Slight  ascending  angio- 
cholitis  with  moderate  sclerosis  of  the  large  spaces;  the  small 
spaces  present  a  very  slight  porto-biliary  embryonic  infiltration. 
The  capillaries,  very  much  distended,  are  engorged  with  blood. 
The  blood  itself  is  extravasated  at  various  points  and  forms  little 
circular  hemorrhagic  centres,  especially  at  the  junction  of  the  cen- 
tral veins.  The  cells  are  entirely  degenerated  and  compressed 
laterally  by  the  distended  capillaries. 

Microscopical  Examination  of  the  Kidneys. — Epithelial  altera- 
tion comparable  to  that  of  the  kidneys  of  the  animal  of  the  pre- 
ceding experiment. 

COLI-TOXIN. 

By  coli-toxin,  I  understand  the  product  obtained  by  the  filtra- 
tion of  bouillon  cultures  of  the  Bacterium  coli  communis.  When 
these  experiments  were  made  I  was  not  sufificiently  well  equipped 
to  be  able  to  manufacture  a  very  large  quantity  of  these  filtered 
cultures  ;  also  I  was  compelled  to  keep  the  coli-toxin  of  the  48 
hour  cultures  for  the  experiments  which  I  had  simultaneously 
undertaken  in  order  to  demonstrate  the  hypo-thermic  action  of 
cultures  of  bacillus  coli  living  and  filtered. 

To  the  rabbits  under  experiment  I  have  administered  by  way 
of  the  mouth  the  filtrates  of  cultures  eight  days  and  a 
month  old.  Everything  leads  me  to  believe  that  the  toxins 
of  cultures  a  little  old  are  less  active  than  those  of  recent 
cultures.  It  was  then  preferable  to  have  recourse  to  the 
former  in  order  to  keep  the  animals  a  longer  time  under  experi- 
ment and  consequently  to  approximate  more  closely  to  the  con- 
dition of  a  patient  through  whose  liver  are  daily  passing  small 
amounts  of  coli-bacillary  poison  elaborated  in  his  intestine.    With 


1 20  The  Liver  of  Dyspeptics. 

the  living  cultures  of  bacillus  coli  I  gave  no  alcohol,  fearing  that 
it  might  affect  in  some  way  the  vitality  of  the  culture.  With 
coli-toxin,  I  thought  there  was  no  objection  to  administering  both 
it  and  alcohol  at  the  same  time  to  some  rabbits.  The  cultures  of 
bacillus  coli  were  filtered  through  Chamberland  filters  under  mer- 
curial pressure,  employing  an  apparatus  manufactured  for  me  by 
Alvergniat  Bros.  After  each  filtration,  we  assured  ourselves,  both 
by  direct  examination  and  cultures,  that  the  filtrate  contained  no 
bacilli :  if  necessary  a  second  filtration  through  the  porcelain  filter 
gave  a  liquid  absolutely  sterile.  The  toxins  obtained  were  pre- 
served in  Roux's  oven,  and  if,  perchance,  they  happened  to  grow, 
we  immediately  stopped  their  use. 

Experiment  xxxiv. 

COLI-TOXIN  8  Days  Old. — Duration :  one  month,  six  days. — 
Rabbit  of  1850  grams,  commencing  June  4,  1893,  takes  daily  half 
a  cubic  centimetre  of  coli-toxin.  June  26th,  the  animal  weighs 
1685  grams.  Commencing  at  this  time  the  dose  was  raised  to  2 
CO.  The  rabbit  died  July  loth  at  10  A.M.,  weighing  only  1240 
grams  and  with  a  temperature  of  35°.  8  C. 

A  utopsy. 

Liver  weighs  49  grams.  Color  pure  brown.  Manifest  conges- 
tion. Nothing  particular  about  the  stomach  or  intestine.  Urine, 
slightly  acid,  contains  neither  sugar,  albumin,  nor  urobilin. 

Microscopic  Exainination  of  the  Liver. — Slight  ascending  angio- 
cholitis ;  in  the  small  and  medium  portal  spaces,  slight  porto-bil- 
iary  embryonic  connective-tissue  proliferation  which  we  also  find 
on  a  goodly  number  of  supra-hepatic  veins.  The  cellular  altera- 
tions are  absolutely  comparable  to  those  of  the  livers  of  the  rab- 
bits previously  examined  which  took  living  cultures.  The  capil- 
laries are  dilated  and  filled  with  blood  globules,  especially  in  the 
direct  vicinity  of  the  central  veins  or  of  the  large  supra-hepatic 
veins. 

Experiment  xxxv. 

CoLi-ToxiN  OF  8  Days  and  Alcohol. — Duration :  one  month 
five  days. — Rabbit  of  1930  grams,  beginning  June  4,  1893,  takes 
daily  half  a  cubic  centimetre  of  toxin  and  20  c.c.  of  alcohol.  It 
was  found  dead  on  the  morning  of  July  loth,  weighing  1500 
grams. 


Personal  Experiments.  121 

Autopsy. 

Zzz^fr  weighs  51  grams;  it  is  reddish-brown,  very  much  con- 
gested. The  stomach  is  marbled  and  streaked  with  red  Hnes  ;  the 
intestine  presents  some  ecchymoses.  The  urine  is  straw-color, 
limpid,  slightly  acid,  and  contains  a  little  albumin. 

Microscopic  Examination  of  the  Liver. — Slight  ascending  angio- 
cholitis  with  very  pronounced  sclerosis  of  the  large  trunks.  A 
veritable  sanguineous  inundation  of  the  liver,  to  such  an  extent 
are  the  capillaries  distended  and  gorged  with  blood  ;  there  are 
some  places  where  there  is  a  true  rupture,  turning  the  cells  topsy- 
turvy and  lacerating  the  hepatic  tissue. 

Some  vessels  of  a  certain  calibre,  completely  filled  with  red 
globules,  contain  networks  of  fibrin.  As  to  the  cells,  they  are 
reduced  almost  to  their  nuclei  at  the  points  where  the  capillary 
distension  is  extreme,  where  the  trabecular  arrangement  is  still 
preserved  ;  elsewhere  they  have  completely  disappeared,  proto- 
plasm and  nucleus ;  we  find  only  a  mass  of  granulations  more 
or  less  dark,  mingled  with  red  globules.  In  a  few  cellular  groups 
only  there  is  a  little  fatty  degeneration. 

Experiment  xxxvi. 
COLI-TOXIN  OF  I  MONTH. — Duration  :  one  month,  six  days. — 
Rabbit  of  1360  grams,  commencing  May  27,  1893,  takes  daily 
half  a  cubic  centimetre  of  coli-toxin.  June  26th,  the  animal 
weighs  1 170  grams.  At  this  date  the  amount  of  toxin  was  in- 
creased to  2  c.c.  On  the  morning  of  July  3d,  the  animal  was 
found  dead,  weighing  1000  grams. 

Autopsy. 

Liver  weighs  28.5  grams.  Dark  brown,  congested.  The 
stomach  is  contracted  without  apparent  alteration.  The  lungs 
are  very  much  congested. 

Microscopic  Examination  of  the  Liver, — Ascending  angiocholi- 
tis  with  very  extensive  intense  sclerosis  of  the  large  spaces.  In 
the  small  and  medium  spaces,  porto-biliary  embryonic  connective- 
tissue  proliferation.  Capillary  dilatation  and  sanguineous  stasis 
less  pronounced  than  in  the  preceding  livers  ;  no  hemorrhagic 
centres.     Always  the  same  cellular  alterations. 

Experiment  xxxvii. 
At  First  Intra-venous  Injection  of  2o-Day  Coli-Toxin, 
THEN  Coli-Toxin  of  i  Month. — Duration:  one  month,  fourteen 


122  The  Liver  of  Dyspeptics. 

days. — Rabbit  of  1770  grams  received  in  the  vein  of  the  ear 
4  c.c.  of  20-day  coli-toxin  ;  he  stood  the  injection  but  grew 
thin.  On  July  5th,  he  was  better,  weighing  1675  grams.  Be- 
ginning at  this  date  he  daily  took  a  i  c.c.  of  i-month  coli-toxin. 
The  supply  of  coli-toxin  being  exhausted  July  nth,  he  went  13 
days  without  taking  any.  He  continued,  nevertheless,  to  grow 
thin:  weight,  1450  grams  July  nth;  July  21st,  ino  grams. 
From  July  24th  to  July  27th,  when  he  died  in  a  state  of  hypo- 
thermia, he  daily  took  i  c.c.  of  toxin.  At  9  A.M.,  the  rectal 
temperature  was  34°. 5  C.     Died  at  2  P.M.,  weighing  850  grams. 

Autopsy. 

Liver  weighs  22  grams.  Kidneys  very  large.  Stomach  pre- 
sents nothing  abnormal.  Lungs  very  much  congested.  No 
urine. 

Microscopic  Examination  of  Liver. — Very  slight  ascending 
angiocholitis  with  moderate  biliary  sclerosis  of  the  large  trunks. 
No  embryonic  proliferation.  Capillary  inflammation  more  marked 
than  in  all  the  previous  livers;  congestion  of  medium  intensity; 
no  hemorrhages.  Cellular  alterations  of  the  same  nature  as  in 
the  other  experiments  with  bacillus  coli  and  coli-toxin. 

Microscopic  Examination  of  the  Kidneys. — Cloudy  swelling  of 
the  epithelium.     Very  pronounced  capillary  inflammation. 

Microscopic  Examination  of  the  Lungs. — The  alveoli  are  filled 
with  blood.  There  is  a  very  intense  capillary  inflammation.  The 
walls  of  the  extra-lobular  branches  of  the  pulmonary  artery  are 
markedly  thickened. 

Experiment  xxxvm. 

COLi-ToxiN  AND  Alcohol. — Duration  :  one  month. — Rabbit 
of  1565  grams,  beginning  May  27,  1893,  daily  takes  half  a  cubic 
centimetre  of  a  one-month  culture  of  coli-toxin  with  10  c.c.  of 
95  per  cent,  alcohol.  The  animal  was  found  dead  at  3  P.M.  June 
26th.     It  weighed  1300  grams. 

A  utopsy. 

Liver  weighs  43  grams,  light  brown.  The  mucous  membrane 
of  the  stomach  is  sown  with  little  punctiform  hemorrhages  which 
give  to  it  a  general  reddish-brown  appearance.  The  intestine 
appears  normal.  The  lungs  are  congested  ;  there  is  a  hemorrhagic 
centre  at  the  base  of  the  left  lung. 


Personal  Experimen  ts.  123 

Microscopic  Exmnination  of  the  Liver. — Ascending  angiocholi- 
tis  with  moderate  sclerosis  of  the  large  trunks.  Embryonic  pro- 
liferation of  the  medium  and  small  portal  spaces,  rings  of  sclerosis 
on  some,  as  plainly  venous  as  biliary.  Cellular  alterations  similar 
to  those  of  the  preceding  livers.  No  fatty  degeneration.  Capil- 
laries moderately  distended  with  blood,  especially  about  the 
central  vein. 

Experiment  xxxix. 

COLI-TOXIN  AND  Alcohol. — Duration  :  two  months,  eight 
days. — Rabbit  of  1930  grams,  beginning  on  June  28,  1893,  takes 
dail}''  2  c.c.  of  a  one-month  culture  of  coli-toxin  and  20  c.c.  of 
95  per  cent,  alcohol.  July  nth,  he  weighs  1625  grams.  The 
toxin  being  exhausted,  until  the  end  he  took  nothing  but  alcohol. 
Nevertheless  he  continued  to  grow  thin  and  died  September  5th, 
weighing  1020  grams. 

Autopsy. 

Liver  weighs  20  grams  ;  it  is  the  color  of  the  lees  of  wine. 
Stomach:  some  ecchymoses  on  the  mucous  membrane. 

Microscopic  Examination  of  tJie  Liver. — Absolutely  comparable 
to  that  of  the  preceding  liver.     No  fatty  degeneration. 

Experiment  xl. 

COLI-TOXIN  AND  Alcohol. — Duration  :  eight  days. — Rabbit 
of  1645  grams  daily  takes,  commencing  May  25,  1893,  half  a 
cubic  centimetre  of  a  one-month  culture  of  coli-toxin  and  ID 
c.c.  of  alcohol.  On  June  ist,  he  weighs  1330  grams.  He  be- 
came cold  without  having  any  convulsive  action.  At  5.30  P.M., 
the  rectal  temperature  was  35°.4  C.  ;  at  8  P.M.,  34°.!  C.  Died  at 
8.45  P.M. 

A  utopsy. 

Liver  weighs  45  grams  ;  dark  colored,  congested.  Stomach 
and  intestine:  mucous  membrane  simply  colored  a  dark  red 
without  ecchymoses.  Kidneys  appear  normal  to  the  naked  eye. 
The  bladder  is  very  full  of  a  slightly  muddy  urine,  somewhat  col- 
ored, which  contains  albumin  but  no  sugar  or  urobilin. 

Microscopic  Examination  of  the  Liver. —  Similar  to  the  pre- 
ceding livers  ;  but  the  cellular  destruction  is  more  general  and 
more  complete ;  the  nuclei  themselves  remain  extremely  pale 
with  various  reagents.     No  fatty  degeneration. 


124  TJie  Liver  of  Dyspeptics. 

HUMAN  FiECES. 

As  a  corollar}',  as  a  synthesis  rather  of  the  action  of  various 
noxious  substances  contained  in  the  intestine,  it  was  deemed  ad- 
visable to  study  the  effect  of  the  absorption  of  fsecal  matters. 
As  we  could  not  think  of  giving  them  to  the  animals  in  kind,  an 
extract  was  prepared  which  we  have  succeeded  in  administering 
to  the  rabbits  by  mixing  it  with  some  bran. 

A  faecal  mass  from  a  man  in  perfect  health  was  thoroughly 
desiccated,  pulverized,  then  treated  with  ether  to  remove  any 
fattv  matters  which  it  might  contain,  and  the  residue  exhausted 
with  alcohol.  This  alcoholic  residue  was  afterwards  reduced  to 
an  extract  by  evaporation.  The  entire  operation  was  repeated 
whenever  the  supply  of  extract  was  exhausted. 

Experiment  xli. 

Extract  of  F^CES. — Duration :  one  month,  two  days. — Rab- 
bit of  1680  grams,  commencing  June  13,  1893,  daily  ingests  2 
grams  of  extract  of  fsces.  He  was  found  dead  on  the  morning  of 
July  15th,  weighing  only  965  grams. 

Autopsy. 

Liver  weighs  23  grams.  The  color  is  all  but  normal.  It  is 
hard  upon  section  and  presents  on  the  surface  some  little  white 
star-shaped  tracts.  There  is  no  alteration  of  the  stomach  or  intes- 
tine.    The  kidneys  and  spleen  are  ven,''  small. 

Microscopic  Exaitiination  of  the  Liver. — No  ascending  angio- 
cholitis.  The  medium-sized  and  small  portal  spaces  are  the  seat 
of  an  embr^^onic  connective-tissue  hyperplasia.  The  capillaries 
are  gorged  with  blood.  Numerous  intra-parenchymatous  hemor- 
rhages. Ver>'  profound  cellular  lesions  comparable  to  those  of 
the  livers  of  bacillus  coli  or  coli-toxin. 

Microscopic  Exaviijiation  of  the  Kidneys. — Cloudy  swelling  of 
the  epithelium.     Commencing  capillary  inflammation. 

Microscopic  Examination  of  Ltings. — Intense  congestion  ;  there 
are  no  hemorrhages,  but  the  alveoli  are  full  of  red  globules. 

Experiment  xlii. 

Extract  of  F.ECES. — Duration  :  twelve  days. — Rabbit  of 
1680  grams  was  subjected  to  the  same  regime  as  the  preceding 


Recapitulation.  125 

one,  commencing  July  19,  1893.     He  died  August  ist,  weighing 
1460  grams. 

Autopsy. 

Liver  weighs  59  grams.  The  lungs  are  congested.  Nothing 
abnormal  in  the  other  organs. 

Microscopical  Examination  of  Liver,  Kidneys,  and  Lungs. — In 
all  points  comparable  to  the  preceding. 

Experiment  xliii. 

Extract  of  F^CE5. — Duration  .•  one  month,  twenty-eight  days. 
— Rabbit  of  1970  grams  ingested  2  grams  of  faecal  extract  daily, 

beginning  August  5,   1893.     He  died  on  October  3d,  at  5  P.M., 
weighing  1200  grams. 

Autopsy. 

Liver  weighs  30  grams  ;  it  is  a  reddish-brown  color.  Lungs 
very  much  congested.     Nothing  particular  in  the  other  organs. 

Microscopic  Examination  of  Liver,  Kidjieys,  and  Lungs, — En- 
tirely similar  to  the  preceding. 

Recapitulation. 

If  we  will  refer  to  Experiment  I,  we  will  see  that  butyric  acid, 
of  itself  alone,  is  capable  of  determining  lesions  in  the  Hver  which 
experimentally  realize  the  atrophic  cirrhosis  of  I^cennec.  Lactic 
and  valerianic  acids  have  given  less  complete  results,  less  absolute, 
but  entirely  of  the  same  order  ;  acetic  acid  has  Hkewise  produced 
a  very  pronounced  cirrhosis,  and  it  is,  of  these  four  agents,  that 
one  which  I  would  be  led  to  consider  as  endowed  with  the  great- 
est sclerogenic  power.  In  fact,  whilst  we  have  been  able  to  ad- 
minister butyric  acid  for  the  space  of  three  months,  acetic  acid, 
moreover  very  much  disliked  by  the  animals,  has  produced,  in 
thirty-six  days,  lesions  almost  as  extensive  as  butyric  acid.  It 
also  destroys  the  animals  more  rapidly  than  the  latter  substance, 
as  its  action  upon  the  hepatic  cell  is  much  more  toxic. 

Of  all  the  poisons  of  the  ahmentary  canal,  acetic  acid  is  the 
most  dangerous,  since  it  is  to  a  high  degree  both  irritating  and 
degenerating.     The  cirrhosis  produced  is  both  venous  and  biliary. 

As  I  have  previously  said,  let  a  noxious  substance,  irritant  to 
the  vessels,  daily  arrive  at  the  liver  in  ver\'  small  quantity : 
under  such  circumstances,  the  cell  has  ample  time  and  force  to 


126  The  Liver  of  Dyspeptics. 

annihilate  it  as  it  arrives,  the  injurious  action  being  confined  to 
the  blood-vessels,  perhaps  to  the  capillaries  alone. 

But  let  the  toxic  substance  be  transported  there  in  larger 
quantity,  it  surprises,  in  some  sort,  the  cell  impotent  to  transform 
this  poison,  which  affects  it  either  functionally,  or  organically  by 
producing  its  degeneration.  The  poison  then  passes  freely  into 
the  circulation  and  also  into  thq  biliary  passages,  there  inducing 
descending  angiocholitis,  the  small  vessels  being  first  affected. 

This  is  the  cause  of  the  canalicular  neo-formation,  which  we 
find  in  infectious  livers  especially,  and  which  may  also  take  place 
in  toxic  livers.  Such  is  the  line  of  union  of  the  poisons  and  the 
toxins,  of  the  chemical  and  the  living  agent,  their  ultimate  action 
being  analogous,  as  many  cases  daily  demonstrate,  and  which  we 
see  in  so  evident  a  manner,  for  the  liver  itself,  in  the  grave  icterus 
which  phosphorus  and  the  various  microbes,  specific  or  not,  en- 
countered in  this  disease,  may  produce  through  the  destruction 
of  the  hepatic  cells. 

The  fatty  acids  proper  have  not  induced  the  least  connective- 
tissue  proliferation.  I  have  above  remarked  that  several  of  the 
rabbits  died  of  tuberculosis.  These  were  more  especially  the 
animals  which  took  the  fatty  acids :  butyric,  valerianic,  and  lactic 
acids,  but  with  no  alcohol.  In  addition,  these  rabbits  were  less 
vigorous  than  the  others,  which  were  expressly  selected,  the 
finest  animals  being  reserved  for  the  ingestion  of  various  sub- 
stances with  alcohol. 

I  have  believed  it  to  be  unnecessary  to  report  these  cases 
here.  I  have,  however,  preserved  one  of  them  (Exp.  XVI.),  which 
seems  to  me  to  show  quite  clearly  that  (which  the  other  experi- 
ments cause  me,  if  not  to  admit,  at  least  to  suspect)  the  constant 
or  frequent  presence  of  fatty  acids  or  acids  of  fermentation  in  the 
alimentary  canal  greatly  favors  a  possible  tuberculization. 

The  rabbit  of  Exp.  XVI.  lived  for  eight  months  and  twenty- 
six  days  after  it  began  to  take  the  fatty  acids,  and,  save  a  transient 
loss  of  v/eight  a  few  days  after  the  commencement  of  this  unusual 
diet,  and  a  second  diminution,  likewise  temporary,  after  an  increase 
of  the  amount  of  fatty  acids  administered,  the  animal  remained 
vigorous  and  of  fine  appearance.  Notwithstanding  its  vigor  and 
its  more  favorable  conditions  of  nourishment  and  hygiene  (save 
liberty),  it  became  tuberculous  at  the  end  of  eight  months,  and 
death  took  place  a  month  afterwards.  The  other  rabbits  were 
less  resistant  and  their  history  is  less  interesting.     Moreover,  it  is 


Recapitulation.  1 2  7 

to  be  remarked  that  most  of  the  tubercles  were  found  in  the 
lungs  ;  there  were  some  also  in  the  liver,  but  a  much  smaller 
number ;  which  signifies  that,  notwithstanding  the  unhealthy- 
condition  of  the  hepatic  cells,  certainly  anterior  to  the  beginning 
of  the  tuberculization,  the  liver  was  not  the  principal  point  of 
attack  of  the  tuberculosis.  Must  we  conclude  from  this  that  gas- 
tro-intestinal  disturbances  predispose  to  tuberculosis  ;  that  the 
initial  gastric  syndrome  of  the  tuberculous,  investigated  by  M. 
Marfan,  is  not  the  effect  of  an  incipient  tuberculosis,  but  a  pre- 
tuberculous  condition  determining  the  invasion  of  the  organism 
by  the  bacillus  of  Koch  ? 

This  would  be  exaggerating  things  very  much  and,  it  seems  to 
me  that  we  may  be  scrupulously  exact,  if  we  recognize  the  fact 
that  dyspeptic  conditions  favor  tuberculization  with  predisposed 
persons,  with  those  individuals  whose  primitive  defect  is  mani- 
fested by  the  congenital  malformations  or  the  arrests  of  develop- 
ment which  we  encounter  with  the  tuberculous :  narrowness  of 
chest  and  thoracic  malformations,  osseous  system  imperfectly  de- 
veloped, lack  of  cardiac  and  arterial  development. 

As  to  the  gastric  syndrome  of  M.  Marfan,  it  may  be  only  an 
exaggeration,  under  the  influence  of  the  commencing  tuberculo- 
sis, of  the  anterior  dyspeptic  troubles,  which  have  probably 
favored  the  germination  of  the  tuberculosis  in  the  prepared  soil. 
We  have  here  again  the  vicious  circle  which  we  encounter  when- 
ever it  is  a  question  of  studying  the  reciprocal  relations  of  two 
functional  disturbances ;  and  always  we  ask  ourselves  the  same 
question,  sometimes  easy  to  answer,  sometimes  unanswerable  :  in 
which  organ  did  the  disturbance  commence?  It  is  the  history  of 
the  influence  of  gastro-intestinal  diseases  upon  the  liver  and  of 
diseases  of  the  liver  upon  the  condition  of  the  alimentary  canal. 
We  may  encounter  some  cases  in  which  it  will  be  a  very  difficult 
matter  to  determine  the  responsibility  of  the  liver  or  of  the  intes- 
tine. With  cirrhosis  itself,  the  common  cirrhosis  of  drunkards,  we 
have  seen  that  the  gastric  disturbances,  which  form  a  portion  of 
the  minor  symptoms  of  Hanot,  can  only  be  an  exaggeration,  under 
the  influence  of  the  commencing  hepatic  affection,  of  anterior  dys- 
peptic troubles  provoked  by  alcoholic  drinks,  and  which  have 
favored,  if  not  determined,  the  sclerosis  and  the  degeneration  of 
the  liver. 

To  return  to  tuberculosis,  it  is  certain  that,  this  disease  once 
established  and  the  digestive  disturbances  confirmed,  the  hepatic 


128  The  Liver  of  Dyspeptics. 

gland  has  to  suffer  greatly  from  the  products  of  defective  diges- 
tion, as  much  as  from  the  presence  in  the  organism  of  the  various 
microbian  toxins  (toxin  of  tuberculosis  and  the  toxins  of  the 
secondary  microbes)  which  are  there  elaborated. 

In  the  chapter  on  pathological  anatomy,  we  have  seen  how  the 
dyspeptic  cirrhosis,  which  I  have  described,  has  some  analogies, 
from  the  point  of  view  of  the  location  of  the  sclerosis,  with  that 
form  of  the  liver  of  the  tuberculous  called :  fatty  hypertrophic 
cirrhosis. 

Acetone  quicklj^  destroyed  three  rabbits ;  two  in  seven  days 
with  a  dose  of  lo  c.c,  one  in  sixteen  days  with  a  dose  of  4  c.c. 
The  lesion  invariably  present  was  an  epithelial  nephritis,  which 
Ebstein  and  Straus  have  described  in  connection  with  diabetes,  a 
sort  of  necrotic  coagulation  manifesting  itself  during  life  by  a 
marked  albuminuria.  It  is  this  acetonic  nephritis  which  Albertoni 
and  Pisenti '  have  experimentally  produced  with  dogs  and  rab- 
bits. 

In  my  preparations  I  have  not  met  with  the  hyaline  degenera- 
tion noticed  with  diabetics  by  Armanni  and  Ehrlich.  As  to  the 
liver,  we  have  been  able  to  see  that,  with  the  two  animals  which 
took  10  c.c.  of  acetone  and  which  were  undoubtedly  destroyed  by 
nephritis,  the  lesions  solely  affected  the  cells.  These  same  lesions 
were  at  their  maximum  with  the  rabbit  which  lived  sixteen  days, 
taking  4  c.c.  of  acetone  daily,  but  besides,  there  was  a  certain  de- 
gree, very  appreciable  in  some  portal  spaces,  of  embryonic  infiltra- 
tion, as  much  venous  as  biliary. 

By  diminishing  the  daily  amount  of  acetone,  after  repeated 
trials,  we  might  succeed  in  so  disposing  the  cell  as  to  make  possi- 
ble the  production  of  a  cirrhosis.  From  thence  to  affirming  that 
diabetic  cirrhosis  may  recognize  such  an  origin,  is  too  great  a  dis- 
tance for  me  to  leap,  at  least  just  at  present. 

The  examination  of  the  organs  of  the  rabbits  poisoned  by 
acetone  has  enabled  me  to  see  some  other  details  which  I  have 
purposely  kept  in  the  background,  waiting  an  opportunity  to  make 
a  more  careful  investigation  of  the  subject. 

Aldehyde  has  proven  itself  to  be  a  substance  with  a  feeble 
sclerosing  action,  but  as  a  poison  of  the  hepatic  cell,  we  would 
be  tempted  to  connect  it  with  alcohol,  only  the  latter  substance 
has  a  fat-producing  action,  whilst  aldehyde  induces  a  granular 
degeneration. 

'  Cf.  Pisenti  e  Acri,  "  Rene  Diabetico,"  Ace.  med.  chir.  d.  Perugia,  1890. 


Recapitulation.  1 29 

Oxalic  acid  induces  gastro-intestinal  inflammation  and  conse- 
quently favors  the  production  of  ascending  angiocholitis.  But 
eventually  it  appears  to  have  an  irritative  action  upon  the  portal 
vessels,  as  is  proven  by  a  certain  degree  of  sclerosis  of  the  small 
spaces.  On  the  other  hand,  it  destroys  the  hepatic  cells,  which 
die  in  a  condition  of  granular  degeneration.  It  also  rapidly  pro- 
duces parenchymatous  nephritis,  so  that,  in  order  to  produce  a 
sclerosis  of  any  importance,  it  would  be  necessary  to  administer 
very  small  doses  of  the  acid  and  keep  up  its  administration  for  a 
very  long  time, 

Budd  and  Virchow  have  deservedly  incriminated  pepper  as  a 
cause  of  cirrhosis.  With  the  rabbit,  in  a  month's  time  it  pro- 
duced a  decided  porto-biliary  sclerosis  with  tendency  to  penetra- 
tion of  the  lobules,  and  it  also  induced  a  fatty  degeneration  of  the 
hepatic  cells.  It  likewise  acts  upon  the  kidneys,  producing  a 
necrosis  of  the  epithelium  and  a  capillary  inflammation  with 
embryonic  connective-tissue  proliferation. 

The  action,  common  to  the  living  cultures  of  Bacterium,  coli 
and  to  the  various  coli-toxins  employed  in  the  experiments,  may 
be  summarized  in  the  following  terms:  production,  all  but  con- 
stant, of  an  ascending  angiocholitis  with  rapid  and  extensive 
sclerosis  of  the  large  portal  spaces  ; — manifest  irritative  action 
upon  the  portal  vessels  of  small  and  medium  calibre,  which  some- 
times present  some  endoarteritis,  sometimes  a  limited  sclerosis, 
almost  always  an  embryonic  infiltration  more  or  less  discrete;  the 
supra-hepatic  veins  themselves  may  participate  in  this  process ; 
the  result  of  this  irritative  action  is  again  found  in  the  biliary 
canals  of  the  same  spaces  ; — tendency  to  capillary  inflammation 
and,  according  to  the  amount  administered  and  the  suddenness 
rather  than  the  duration  of  the  action,  an  intense  congestion  and 
hemorrhages  not  only  in  the  liver,  but  also  in  the  kidneys  and 
especially  in  the  lungs  ; — granular  necrosis  of  the  hepatic  cells  with 
vesicular  condition  of  the  nuclei  when  the  action  has  been  pro- 
found and  rapid,  or  simply  granular  degeneration  of  the  proto- 
plasm with  nuclear  irritation  if  the  action  has  been  less  sudden 
and  more  prolonged  ; — lastly,  in  the  cases  in  which  the  toxi-infec- 
tion  has  been  rapid  and  severe,  production  of  ecchymoses  upon 
the  gastro-intestinal  mucous  membrane. 

The  ascending  angiocholitis  has  its  raisoii  (Titre  in  the  greater 
virulence  of  the  bacillus  coli  introduced,  and,  if  we  are  experi- 
menting with  coli-toxin,  in  the  increase  of  virulence  which  its 


130  Hie  Liver  of  Dyspeptics. 

arrival  in  the  alimentary  canal  produces  in  the  micro-organisms 
which  normally  inhabit  it;  in  both  cases,  the  greater  vitality  of 
the  microbe,  added  to  a  weakening  of  the  hepatic  function  under 
the  influence  of  the  poisons  absorbed,  is  the  cause  of  the  invasion 
of  the  choledochus,  so  arranged,  with  the  rabbit  especially,  as  to 
give  an  asylum  to  the  normal  or  abnormal  guests  of  the  intestine. 

The  capillary  inflammation  is  much  more  pronounced  and  is 
generalized  in  the  other  organs  if,  instead  of  causing  the  animals  to 
ingest  the  culture  and  especially  the  toxin,  we  inject  it  into  the 
veins.  We  may  convince  ourselves  of  this  fact  by  referring  to 
Exp.  XXXVII.  Some  other  experiments  which  I  have  not  here 
reported,  in  which  venous  injection  was  employed,  have  given  the 
same  results.  So  if,  for  one  reason  or  another,  small  amount  or 
greater  resistance,  the  hepatic  cell  succeeds  in  escaping  the 
necrosing  action  of  the  coli-toxin,  the  ultimate  effect  of  this 
microbian  poison  is  to  produce  not  only  hepatic  cirrhosis,  but,  in 
addition,  sclerosis  of  the  whole  vascular  system.  Extract  of  faeces 
has  given  results  comparable  to  those  of  coli-toxin. 

I  now  come  to  the  role  which  alcohol  has  played  in  these 
experiments.  With  the  preconceived  idea  that  it  would  add  its 
noxious  action  to  that  of  the  various  substances  ingested,  I  pur- 
posely selected  the  fattest  and  most  vigorous  animals,  in  order 
that  the  experiment  might  last  as  long  as  possible.  It  has  hap- 
pened that,  not  only  all  the  animals,  which  took  alcohol  in 
addition  to  the  poisonous  chemicals,  have  lived  a  very  much 
longer  time  than  those  not  taking  it,  a  year  and  more,  but  like- 
wise the  sclerosis  was  infinitely  less,  sometimes  entirely  absent. 

The  cellular  destruction,  caused  by  the  toxic  agent  adminis- 
tered with  the  alcohol,  was  not  produced  so  rapidly,  and  in  all 
the  cases,  the  dominant  lesion  has  been  the  steatosis.  It  would 
seem  as  if  the  alcohol  had  neutrahzed,  I  know  not  how,  the 
poison  administered,  as  if  it  had  strengthened  the  organism  and 
the  liver  itself,  as  if  it  had  reserved  for  itself  the  right  of  slowly 
destroying  the  hepatic  cell,  and  in  its  own  way.  It  is  very  diffi- 
cult to  state  precisely  the  determinism  of  such  a  fact.  The 
cause  of  it  is  not  to  be  found  in  the  greater  individual  resistance 
of  the  selected  animals. 

All  the  organic  acids  are  but  slightly  soluble  in  alcohol,  it  is 
true;  some  only  dissolve  in  boiling  alcohol  itself.  Perhaps  this 
is  the  reason  for  their  direct  passage  into  the  fasces  and  of  their 
arrival  at  the  liver  in  very  small  quantity.     Possibly  also,  the 


Recapitulation.  131 

alcohol,  coagulating  the  stomachal  and  intestinal  mucus,  or  the 
albuminoid  substances  of  the  ingesta,  has  been  included  in  the 
coagulum  and  expelled  with  the  faecal  matters. 

I  hasten  to  add  that  nothing  similar  happened  with  the  ani- 
mals which  ingested  coli-toxin  and  alcohol  at  the  same  time. 
The  latter  substance  apparently  had  no  effect,  undoubtedly  on 
account  of  the  great  noxiousness  of  the  substance  with  which 
it  was  associated.  A  very  valuable  lesson  is  to  be  derived  from 
these  experiments ;  it  is  that  alcohol  addresses  itself  especially  to 
the  hepatic  cell,  for  which  it  is  essentially  steatogenic.  This  action 
is  only  slowly  produced  and  at  the  expiration  of  a  long  period. 
This  corroborates  the  conclusions  of  previous  experimenters, 
namely :  first,  that  moderate  amounts  of  alcohol,  far  from  having 
an  injurious  action  upon  the  organism,  and  in  particular  upon 
the  liver,  on  the  contrary  aid  in  the  preservation  of  the  general 
health,  and  permit  the  opposing  of  a  greater  resistance  to  the 
different  agents  of  intoxication  or  infection.  Second,  that  large 
amounts  of  alcohol,  solely  taking  the  liver  into  consideration, 
address  their  toxic  action  almost  exclusively  to  the  hepatic  cells, 
of  which  they  eventually  provoke  a  fatty  degeneration. 

Alcohol  is,  then,  toxic  but  not  irritant  to  the  liver  ;  it  is  so  to  a 
high  degree,  so  far  as  the  mucous  membrane  of  the  stomach  is 
concerned.  The  gastritis  of  drunkards  is  a  thing  so  common 
(whatever  may  be  its  form,  hyperpeptic,  mucous,  ulcerative,  or 
hemorrhagic),  that  it  is  perhaps  to  it  and  not  to  the  alcohol  that 
it  would  be  proper  to  attribute  a  large  number  of  the  so-called 
alcoholic  cirrhoses  ;  the  chronic  gastritis  terminating  in  dilatation 
of  the  stomach  and  alimentary  stasis,  that  is,  in  abnormal  fermen- 
tations. And  moreover,  is  it  principally  alcohol  which  the  so-called 
alcoholic  {ethyliques)  drunkards  drink  ? 

M.  Lancereaux  has  rightly  remarked  that  wine  drinkers  are 
especially  subject  to  cirrhosis.  Now,  in  wine  there  is  only  ten  per 
cent,  of  alcohol,  and,  in  addition,  it  contains  small  amounts  of 
other  substances  with  which  we  do  not  concern  ourselves  :  coloring 
matters,  several  kinds  of  ethers,  aldehydes,  acetones,  and  acetic 
acid.  On  the  other  hand,  once  in  the  stomach,  wine  undergoes 
the  acetic  fermentation.  As  to  drinkers  of  alcohol  in  the  form  of 
brandy,  raw  spirits,  absinthe,  liqueurs,  etc.,  it  is  generally  amylic 
alcohol  which  they  are  in  the  habit  of  drinking  and  with  it  a  large 
quantity  of  essences,  the  toxicity  of  which  is  no  longer  question- 
able, and  from  which  the  stomach  has  more  to  suffer  than  the 


132  The  Liver  of  Dyspeptics. 

liver.  We  know  that  the  alcohol  drunk  by  the  laborers  of  the 
north,  at  Rouen  in  particular,  is  a  heterogeneous  product  and 
horribly  impure,  even  containing  sulphuric  acid. 

Very  many  other  considerations  would  in  addition  plead 
against  the  alcoholic  origin,  at  least  direct,  of  cirrhosis.  But  I 
have  promised  not  to  defend  the  case  of  alcohol,  which  in  truth  is 
not  the  design  of  this  work.  It  is  only  as  a  corollary  of  my  experi- 
ments that  I  have  ventured  the  preceding  reflections.  If  alcohol 
must  disappear  from  the  scene  or  pass  to  a  subordinate  position 
in  the  etiology  of  the  cirrhoses,  may  it  die  a  happy  death. 

We  must  not  fail  to  observe  that  the  substances  employed  in 
our  experiments  have  produced  in  the  liver  of  the  animals,  not  a 
diffused  hypertrophic  cirrhosis  with  mono-cellular  tendency,  as 
we  might  be  led  to  expect  after  reading  the  first  two  parts  of  this 
thesis,  but  an  atrophic  cirrhosis  comparable  to  that  of  Laennec. 
I  cannot  help  this,  and  I  content  myself  with  simply  recording 
the  cases  and  the  facts.  Certain  conditions  which  I  do  not  care 
to  take  under  consideration  at  the  present  time,  as  I  do  not  wish 
to  enter  into  the  domain  of  pure  hypothesis,  perhaps  prescribe 
the  location  of  the  connective-tissue  process. 

Conclusions. 

Of  all  the  preceding  portions  of  this  work,  the  following 
propositions  should  be  retained. 

First,  alcohol  is  not  everything  in  the  etiology  of  cirrhosis  of 
the  liver.  Its  pathogenic  role  demands  a  searching  inquiry,  which 
a  long  term  of  years  can  alone  bring  to  a  successful  termination. 
In  fact,  it  is  indispensable  that  the  condition  of  the  alimentary 
canal  should  be  carefully  investigated  with  those  suffering  from 
cirrhosis,  and  an  attempt  made  to  ascertain  if,  with  them,  fermen- 
tations of  gastrio-intestinal  origin  do  not  give  rise  to  the  pro- 
duction of  substances  which  are  endowed  with  properties  both 
irritating  and  toxic  to  the  liver. 

Second,  entirely  independent  of  the  alcoholic  habit,  we  fre- 
quently encounter  a  pathological  condition  of  the  liver  with  dys- 
peptics, which  is  manifested  by  increase  of  the  size  of  this  organ ; 
it  is  the  dyspeptic  liver. 

Third,  this  increase  of  size  is  temporary  or  permanent.  Tem- 
porary, with  frequent  returns,  it  constitutes  the  hepatic  conges- 
tion noticed  for  a  long  time  by  various  authors,  and  especially 
by  M.  Bouchard.     Permanent,  it  is  dyspeptic  cirrhosis. 


Conclusions.  133 

Fourth^  this  dyspeptic  cirrhosis,  described  for  the  first  time  in 
this  work,  is  manifested  :  clinically,  by  an  enlarged  liver,  smooth, 
remarkably  hard  (like  wood),  without  increase  in  size  of  the  spleen, 
without  icterus,  ascites,  or  development  of  the  collateral  abdomi- 
nal circulation  ;  histologically,  by  a  diffused  generalized  cirrhosis, 
inter-  and  intra-lobular,  with  mono-cellular  tendency,  with  relative 
integrity  of  the  hepatic  cells. 

Fiftky  the  duration  of  such  an  affection  is  very  long,  ten  years 
and  more,  the  size  of  the  liver  remaining  almost  the  same.  The 
termination  may  take  place,  as  in  the  atrophic  cirrhosis  of  Laen- 
nec,  by  exaggeration  of  the  mechanical  interference  and  produc- 
tion of  ascites  and  enlarged  abdominal  veins,  and  also  by  terminal 
infectioiL  The  prognosis  is  then,  as  always,  connected  with  the 
condition  of  the  hepatic  cells. 

Sixth,  among  the  toxic  substances  which  are  elaborated  in  the 
alimentary  canal,  we  must  consider  the  acids  of  fermentation  as 
possessing  a  marked  sclerogenic  action  :  butyric,  lactic,  valerianic, 
and  especially  acetic  acid. 

As  to  coli-toxin,  it  is  probable  that  it  also  has  a  sclerosing 
action  upon  the  liver,  unless  it  reaches  this  organ  in  an  amount 
sufficient  to  rapidly  destroy  the  hepatic  cells. 

Seventh,  we  must  also  take  into  consideration  the  predisposi- 
tion most  frequently  created  by  the  gouty  diathesis  {arthritisme, 
Hanot). 

Eighth,  dyspeptic  cirrhosis  can  only  be  confounded  with  cancer 
of  the  liver,  from  which  it  is  distinguished  by  its  very  long  dura- 
tion ;  or  with  a  large  lithiasic  liver  (Jithiasique),  which  is  most 
frequently  accompanied  by  icterus ;  or  with  an  enlarged  alcoholic 
liver,  with  which  we  will  ordinarily  find  a  large  spleen  and  very 
soon  ascites  and  enlargement  of  the  subcutaneous  abdominal  veins. 

Ninth,  the  treatment  should  be  especially  addressed  to  the 
digestive  functions.  Intestinal  antisepsis  will  be  of  very  great 
assistance,  and  will  give  very  satisfactory  results,  especially  in  the 
congestive  forms.  Calomel,  in  the  dose  of  one  centigram,  may 
be  successfully  prescribed. 

THE  END. 


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